Biomedical subjects

S Shu

Publications and source records attributed to S Shu.

At least 55 records · Page 3Linked to original sources

PubMed1998

Systemic T cell adoptive immunotherapy of malignant gliomas.

OBJECT: To determine the feasibility, toxicity, and potential therapeutic benefits of systemic adoptive immunotherapy, 10 patients with progressive primary or recurrent malignant glioma received this treatment. Adoptive immunotherapy, the transfer of immune T lymphocytes, is capable of mediating the regression of experimental brain tumors in animal models. In animal models, lymph nodes (LNs) that drain the tumor vaccine site are a rich source of tumor-immune T cells. METHODS: In this clinical study, patients were inoculated intradermally with irradiated autologous tumor cells and granulocyte macrophage-colony stimulating factor as an adjuvant. Cells from draining inguinal LNs, surgically resected 7 days after vaccination, were stimulated sequentially with staphylococcal enterotoxin A and anti-CD3, and a low dose of interleukin-2 (60 IU/ml) was used to expand the stimulated cells. The maximum cell proliferation was 350-fold over 10 days of culture. The activated cells were virtually all T cells consisting of various proportions of CD4 and CD8 cells. These cells were given to patients by intravenous infusion at doses ranging from 9 x 10(8) to 1.5 x 10(11). There were no Grade 3 or 4 toxicities associated with the treatment. Following T-cell transfer therapy, radiographic regression that lasted at least 6 months was demonstrated in two patients with recurrent tumors. One patient demonstrated stable disease that has lasted for more than 17 months. The remaining patients had progressive disease; however, four of the eight patients with recurrent tumor remain alive more than 1 year after surgery for recurrence. Three patients required intervention with corticosteroid agents or additional surgery approximately 1 month following cell transfer. CONCLUSIONS: These intriguing clinical observations warrant further trials to determine whether this approach can provide therapeutic benefits and improve survival.

Adjuvants, Immunologic↗

PubMed1997

Tumor immunology.

Malignant tumors express antigens that may stimulate and serve as targets for antitumor immunity. Virally induced tumors usually contain integrated proviral genomes in theircellulargenomes and often express viral genome-encoded proteins that may stimulate specific host immune responses. Antigens unique to individual tumors that stimulate specific rejection of transplanted tumors have been demonstrated only in experimental animals. Other tumor antigens that potentially can stimulate immune responses are shared by different tumors. These include products of mutated or rearranged oncogenes or tumor-suppressor genes. Tumors may also overexpress tissue differentiation antigens or embryonic antigens, which also have the potential to be recognized by the immune system. The recent identification of tumor antigens recognized by cytotoxic T cells opens up new possibilities for constructing chemically defined antigens for specific immunotherapy. Treatment of malignant tumors in humans by immunologic approaches, although theoretically attractive, has not yet succeeded on a large scale. Important progress in immunotherapy of cancer is emerging with several different treatment modalities.

Antigens, Neoplasm↗

PubMed1997

Monocyte chemoattractant protein inhibits the generation of tumor-reactive T cells.

The adoptive transfer of tumor-sensitized T cells can eradicate disseminated malignancy in murine animal models. T cells must be sensitized to tumor antigens in vivo to acquire antitumor reactivity. T-cell sensitization has been demonstrated to be dependent on host antigen-presenting cells. Tumor-associated macrophages are a heterogeneous population of cells that may have both inhibitory and stimulatory influences on the sensitization of naive T cells. Here we demonstrate that a weakly immunogenic tumor, the MCA 205 sarcoma, produces substantial amounts of murine monocyte chemoattractant protein 1 (MCP-1). Neutralization of MCP-1 during in vivo T-cell sensitization resulted in T cells that possessed enhanced therapeutic activity against established pulmonary metastases. These T cells sensitized during MCP-1 depletion also exhibited enhanced production of IFN-gamma upon recognition of tumor targets. These results demonstrate that MCP-1 can have a potent inhibitory influence on the development of tumor-reactive T cells.

Animals↗

PubMed1997

Treatment of murine gliomas by adoptive transfer of ex vivo activated tumor-draining lymph node cells.

The adoptive transfer of tumor-reactive T lymphocytes has recently been demonstrated to be an effective means for mediating the regression of experimental intracranial fibrosarcomas. In this study, mice bearing syngeneic intracranial GL261 gliomas were cured by the combination of sublethal whole body irradiation followed by the intravenous transfer of tumor-draining lymph node (LN) T cells activated with anti-CD3 or staphylococcal enterotoxin C2 (SEC2). To further identify the functional effector T cel population in the adoptive immunotherapy, LN T cells were separated into two subsets, based on the level of expression of the cell adhesion molecule CD62L (L-selectin). As few as 5 x 10(5) CD62Llow cells could cure the majority of animals, whereas 2 x 10(6) CD62Lhigh cells were completely ineffective. Moreover, T cells isolated from advanced intracranial tumors were identified to be predominantly CD62Llow. In contrast, spleens contained a mixture of CD62L low and high cells similar to the transferred cell population. T cells in the glioma site were more actively proliferating than those isolated from the spleen. Mice cured of GL261 tumors demonstrated long-term immunologic memory by rejecting intracranial challenges of the original tumor but not an immunologically distinct tumor. Furthermore, despite infiltration of transferred cells into the intracranial tumors, cured mice did not exhibit any apparent neurologic abnormalities during treatment, prolonged follow-up, or after intracranial tumor rechallenge. This study demonstrates the effective treatment of an intracranial murine glioma by the systemic adoptive transfer of activated tumor-draining LN T cells and selective tumor infiltration by the therapeutically active CD62Llow T cells.

Adoptive Transfer↗

PubMed1997

Treatment of subcutaneous tumor with adoptively transferred T cells.

Adoptive immunotherapy with T cells directed at tumor antigens has been demonstrated to result in the regression of malignant tumors in humans. These encouraging results have prompted the further exploration of parameters necessary to treat tumor in various locations in animal models. We have demonstrated that T cells that are sensitized to tumor antigens and then ex vivo cultured are capable of eradicating pulmonary metastases. In this report, we demonstrate that these T cells are capable of eliminating subcutaneous tumor deposits. Critical to the successful treatment of subcutaneous tumor was treatment with a large number of adoptively transferred T cells and pretreatment of the mice with irradiation. The transfer of T cells from tumor-bearing mice into irradiated mice failed to inhibit the therapeutic effect of ex vivo cultured T cells, suggesting that irradiation was not acting only as an immunosuppressant. Irradiation resulted in increased expression of the F4/80 and 33D1 epitopes on antigen-presenting cells within the tumor. The therapeutic effect of the adoptively transferred T cells was eliminated if either CD4 cells or CD8 cells were depleted. Naive T cells subjected to the same culture conditions were completely ineffective at eliminating tumor. These results demonstrate that adoptively transferred T cells derived from tumor-bearing hosts can treat subcutaneous tumor deposits, and they define the conditions necessary for the elimination of tumor in this location.

Animals↗

PubMed1997

1H-magnetic resonance spectroscopy-determined cerebral lactate and poor neurological outcomes in children with central nervous system disease.

By using proton magnetic resonance spectroscopy ((1)H-MRS), cerebral lactate has been shown to be elevated in a wide variety of pediatric and adult neurological diseases. In this study we compared 36 newborns, infants, and children with elevated lactate peaks on (1)H-MRS with 61 patients without an identifiable lactate signal. (1)H-MRS was acquired from the occipital gray and parietal white matter (8 cm3 volume, STEAM sequence with echo time = 20 msec, repetition time = 3.0 seconds) and data were expressed as ratios of different metabolite peak areas (N-acetylaspartate [NA]/creatine [Cr], NA/choline [Ch], and Ch/Cr) and the presence of a characteristic lactate doublet peak at 1.3 ppm. Outcomes (Pediatric Cerebral Performance Category Scale score; PCPCS) were assigned 6 to 12 months after injury. Patients with lactate peaks were more likely to have suffered a cardiac arrest, were more often hyperglycemic, and had lower Glasgow Coma Scale scores on admission. They were also more likely to have abnormal metabolite ratios when compared with age-matched controls or with patients without detectable lactate. Of prognostic importance, patients with increased lactate were more likely to be severely disabled (39% vs 10%), survive in a persistent vegetative state (13% vs 2%), or have died (39% vs 7%). In contrast, patients with similar conditions without increased lactate were more likely to have had a good outcome (23% vs 3%) or recovered to a mild (38% vs 6%) or moderate disability (20% vs 0%). Our data suggest that (1)H-MRS is useful in the prediction of long-term outcomes in children with neurological disorders. Patients with elevated cerebral lactate are more likely to die acutely or are at greater risk for serious long-term disability.

Brain Diseases↗

PubMed1997

Hemolymph juvenile hormone titers in pupal and adult stages of southwestern corn borer [Diatraea grandiosella (pyralidae)] and relationship with egg development.

Juvenile hormones I, II and III were monitored in hemolymph of pupal and adult stages of various ages of Diatraea grandiosella females. JH III was the predominant homologue followed by JH II, and JH I was rarely detectable. At day 5 after pupation, no JH was detectable. JH titers increased from 7.5days after pupation to a peak of 24.8ngml(-1) JH II and 26ngml(-1) JH III at adult emergence and then declined to low levels by 24h after emergence. Ovarian development in D. grandiosella parallels changes in hemolymph JH titers, but the role of JH in vitellogenesis is unclear since the time of vitellogenesis initiation has yet to be determined. No apparent vitellogenin deposition was observed in eggs 5days after pupation. Some oocytes were partially vitellogenic by 7.5days after pupation and oocytes continued to grow afterwards, but no oocytes were chorionated during the pupal stage. Chorionated oocytes were observed in 24-h-old female moths. Juvenile hormone is essential for chorion formation in this species, because decapitated pupae treated with 10&mgr;g JH III in corn oil developed chorionated oocytes while decapitated pupae treated with corn oil did not.

Journal Article↗

PubMed1997

Secretion of biologically active superantigens by mammalian cells.

The genetic modification of tumor cells to secrete immune regulatory molecules can elicit a potent antitumor immune response. Bacterial superantigens are among the most potent T cell mitogens. Activation of tumor-sensitized T cells by bacterial superantigens can lead to immune effector cells with potent and specific in vivo antitumor activity. Retrovirus vectors encoding for the bacterial superantigens SEA and SEC2 were constructed, and recombinant retrovirus stocks were generated. SEA and SEC2 could be detected in the culture supernatant of tumor cells after a single exposure to retrovirus. Molecular analysis of the genetically modified cells revealed intact proviral DNA and abundant vector-derived superantigen RNA. Biologic activity was apparent for both superantigens. Secretion of biologically active superantigen by mammalian cells has not been reported previously, and this will enable investigating the potential for superantigen gene therapy.

3T3 Cells↗

PubMed1997

Can sensitized lymphocytes retain reactivity to inner ear antigens after retrieval from frozen storage?

Immune inner ear disease results in rapidly progressive, bilateral sensorineural hearing loss and is one of the few forms of sensorineural hearing loss that can be treated medically. The purpose of this study is to identify and preserve several populations of sensitized lymphocytes from patients with immune inner ear disease as a first step toward cloning autoreactive T cells, in order to study the pathogenesis of disease. Lymphocytes from four patients with high reactivity (stimulation index of 2.5 or greater) were placed in frozen storage. At 8 to 14 months they were thawed and restimulated. All four samples were viable. Two reacted again to inner ear homogenate, but with different intensities. Some lymphocytes sensitized to inner ear antigens can retain reactivity after frozen storage. This methodology may be useful to clone highly reactive T cells.

Adolescent↗

PubMed1997

Proton MR spectroscopy after acute central nervous system injury: outcome prediction in neonates, infants, and children.

PURPOSE: To evaluate the usefulness of proton magnetic resonance (MR) spectroscopy in predicting 6-12-month neurologic outcome in children after central nervous system injuries. MATERIALS AND METHODS: Localized single-voxel, 20-msec-echo-time MR spectra (including N-acetylaspartate [NAA], choline [Ch], creatine and phosphocreatine [Cr]) were obtained in the occipital gray matter in 82 patients and 24 control patients. Patient age groups were defined as neonates (< or = 1 month [n = 23]), infants (1-18 months [n = 31]), and children (> or = 18 months [n = 28]). Metabolite ratios and the presence of lactate were determined. Linear discriminant analysis-with admission clinical data, proton MR spectroscopy findings, and MR imaging score (three-point scale based on severity of structural neuroimaging changes)-was performed to help predict outcome in each patient. Findings were then compared with the actual 6-12-month outcome assigned by a pediatric neurologist. RESULTS: Outcome on the basis of proton MR spectroscopy findings combined with clinical data and MR imaging score was predicted correctly in 91% of neonates and in 100% of infants and children. Outcome on the basis of clinical data and MR imaging score alone was 83% in neonates, 84% in infants, and 93% in children. The presence of lactate was significantly higher in patients with poor outcome than in patients with good-moderate outcomes in all three age groups (neonates, 38% vs 5%; infants, 87% vs 5%; children, 64% vs 10% [chi 2 test, P < .02]). In children with poor outcomes, NAA/Cr ratios were significantly lower in infants (P = .006) and children (P < .001), and NAA/Ch ratios were significantly lower in infants (P = .001) and neonates (P = .05). CONCLUSION: Findings at proton MR spectroscopy helped predict long-term neurologic outcomes in children after central nervous system injury.

Adolescent↗

PubMed1997

Adoptive immunotherapy with vaccine-primed lymph node cells secondarily activated with anti-CD3 and interleukin-2.

PURPOSE: In preclinical studies, we have reported the ability to induce immune T cells in lymph nodes (LN) primed by in vivo vaccination with tumor cells admixed with a bacterial adjuvant. These LN cells can be activated and expanded ex vivo for the successful immunotherapy of established tumors. We have applied these methods to generate vaccine-primed LN in patients with advanced melanoma and renal cell cancer (RCC) for therapy. MATERIALS AND METHODS: Irradiated autologous tumor cells admixed with bacille Calmette-Guérin (BCG) were used to vaccinate patients. Seven days later, draining LN were removed for activation with anti-CD3 monoclonal antibody (mAb) followed by expansion in interleukin-2 (IL-2). Activated LN cells were administered intravenously (IV) with the concomitant administration of IL-2. RESULTS: A total of 23 patients were evaluated (11 melanoma and 12 RCC). Vaccine-primed LN were expanded ex vivo with a mean of 8.4 x 10(10) cells administered per patient. Among 20 patients assessed, 15 demonstrated minimal cytotoxicity of autologous tumor cells by the activated LN cells, with the remaining mediating nonspecific cytotoxicity. By contrast, a majority of the activated LN cells showed highly specific release of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon gamma (IFN-gamma) to autologous but not allogeneic tumor stimulation. This tumor-specific cytokine release was found to be major histocompatibility complex (MHC) class I-restricted, which indicates the involvement of CD8+ cells. Among 11 melanoma patients, one had a partial tumor response. Among 12 RCC patients, two had complete and two partial responses. A trend (P = .066) between the enhancement of delayed-type hypersensitivity (DTH) reactivity to autologous tumor after therapy and tumor regression was observed. CONCLUSION: Tumor vaccines can be used to induce immunologically specific T-cell responses against melanoma and RCC in draining LN. Anti-CD3/IL-2 activation of primed LN cells can be reliably performed for clinical therapy and appears to have activity in patients with metastatic RCC.

Adult↗

PubMed1997

[Cultivated technique of high yield for Polygonatum officinale].

By studying cultivated materials, hided crops, cultivated way, applied fertilizer about the cultivation of Polygonatum officinale, put forward following the methods of cultivation of P. officinale. Choose rhizome segments with top buds as plant materials, adopt level rectangular pieces of land in a field width 100 cm, cultivate late-maturing corn as hiding shady, adopt density of 1.5-2.0 ten thousand plants/mu, apply N and P fertilizers in the growth.

Fertilizers↗

PubMed1996

Treatment of intracranial tumors by systemic transfer of superantigen-activated tumor-draining lymph node T cells.

Adoptive transfer of tumor-sensitized T lymphocytes has demonstrated therapeutic efficacy in animal tumor models and in some patients with melanoma and renal cell cancers. In experimental settings, T lymphocytes derived from lymph nodes (LNs) draining progressively growing tumors can be activated ex vivo to generate tumor-reactive lymphocytes with therapeutic efficacy. Despite the theoretical concern regarding inaccessibility of the central nervous system to systemically transferred T cells, our recent experiments demonstrated that anti-CD3-activated tumor-draining LN cells are capable of mediating the regression of established intracerebral tumors. In this study, several staphylococcal enterotoxins (SEs), including SEA, SEC2, and SEE, and exfoliating toxin, known to be superantigens, were tested for their ability to stimulate tumor-draining LN cells to acquire antitumor reactivity for the treatment of intracerebral tumors. SEs bind to the MHC class II molecule and provide an activating signal to T cells bearing particular T-cell receptor Vbeta chains. Tumor-draining LN cells activated with SEs demonstrated selective Vbeta T-cell expansion. In adoptive immunotherapy of intracranial (IC) tumors, SEA-and SEC2-activated cells had the highest efficacy, whereas SEE-activated cells were not therapeutic. Despite the antigen independence of SE activation, the T cells retained immunological specificity for the tumor, which provided the initial in vivo sensitization of the LN. During the ex vivo stimulation with superantigens, both CD4+ and CD8+ T cells proliferated, and both subsets were required to mediate regression of IC tumors. In contrast to the adoptive immunotherapy of visceral tumors, the systemic administration of exogenous interleukin 2 failed to support the antitumor reactivity in mice depleted of CD4 cells, and, in fact, it inhibited the therapeutic efficacy. Furthermore, mice cured of intracerebral tumors by the adoptive transfer of T cells were resistant to an IC tumor rechallenge. However, in contrast to the immunological specificity demonstrated during the primary adoptive transfer, cured mice were able to reject challenge with several immunologically distinct fibrosarcomas but not a melanoma. These results indicate that superantigen-activated LN cells can circulate to and interact with intracerebral tumors mediating tumor regression in an immunologically specific manner. Although conditions that optimize the treatment of intracerebral tumors appear to be different from those for visceral tumors, analysis of T-cell receptor Vbeta expression among cells activated with several superantigens does not reflect a preferential usage of Vbeta gene segments in the immune response to autochthonous tumors.

Animals↗

PubMed1996

Isolation based on L-selectin expression of immune effector T cells derived from tumor-draining lymph nodes.

The ability to generate a large number of tumor-reactive T lymphocytes is the most critical requirement for adoptive immunotherapy. Our laboratory has previously demonstrated that cells from tumor-draining lymph nodes (LNs) are an excellent source of tumor-reactive T lymphocytes. After activation with anti-CD3, these cells readily proliferate in low concentrations of interleukin 2 and acquire effector functions. The adoptive transfer of these cells is capable of mediating the regression of tumors established in the lung as well as in the brain. Here, we analyzed several adhesion molecules on the tumor-draining LN T cells and separated them based on L-selectin expression. The homing receptor L-selectin mediates adhesion to the luminal surface of specialized high endothelial venules, thus regulating lymphocyte recirculation through peripheral LNs. In response to progressive tumor growth, a small population of draining LN T cells down-regulated L-selectin and increased the expression of CD44 and lymphocyte function-associated antigen 1. In adoptive immunotherapy, purified T cells with low L-selectin (L-selectin-) expression constituted all the in vivo antitumor reactivity, whereas isolated high L-selectin (L-selectin+) cells were ineffective. Furthermore, reverse transcription-PCR analysis revealed that L-selectin- cells expressed interleukin 2, IFN-gamma and tumor necrosis factor alpha mRNA upon in vitro stimulation with specific tumor cells. These results suggest that highly potent immune T cells can be isolated based on their pattern of adhesion molecule expression. The ability of the immune effector cells to transcribe cytokine genes when stimulated with tumor cells provides a basis for identifying similar cells for adoptive immunotherapy of cancer in humans.

Animals↗

PubMed1996

Defining the synergistic effects of irradiation and T-cell immunotherapy for murine intracranial tumors.

In recent studies, we demonstrated that the systemic adoptive transfer of tumor-draining lymph node (LN) cells, activated ex vivo with anti-CD3 mAb or bacterial superantigens, was effective for treatment of tumors in the brain, an immunologically privileged site. In this study, we demonstrate that sublethal whole body irradiation (WBI) or local cranial irradiation of the tumor-bearing host prior to the adoptive transfer of LN cells, activated with the superantigen, SEC2, augments therapeutic efficacy, whereas body irradiation with cranial shielding is ineffective. WBI prior to tumor inoculation or treatment of tumor-bearing animals with cyclophosphamide to eliminate suppressor cells did not enhance the therapeutic efficacy of adoptively transferred cells. Analysis of brains by immunohistochemistry, 4 days after cell transfer, revealed a dense infiltrate of SEC2-activated T lymphocytes which exclusively express the T cell receptor V beta 8.2 phenotype, of both CD4 and CD8 subsets, throughout the tumors in both irradiated and nonirradiated animals. In addition, MAC-1+ cells were present within tumors irrespective of either irradiation or cell transfer. These findings demonstrate that the systemically transferred T cells could gain access to the tumor located in the CNS. However, the therapeutic enhancement by sublethal irradiation does not reflect an increase in T cell or MAC-1+ cell migration into the tumor.

Animals↗

PubMed1996

Tumor reactivity of immune T cells in short-term culture.

The adoptive transfer of immune T cells is capable of mediating the regression of established neoplasms in a variety of animal tumor models. The antitumor activity is invariably proportional to the number of cells transferred, thus methods to expand immune cell number while maintaining therapeutic efficacy have been extensively investigated. Here we demonstrate that a short-term culture of immune T cells can amplify the T cell number and enhance the therapeutic reactivity against established pulmonary tumor, while maintaining immunological specificity. In contrast, the therapeutic reactivity of immune T cells against established subcutaneous tumor is diminished by short-term culture. While cultured immune T cells are not cytotoxic in a 4-h Cr-release assay, they do specifically secrete interferon gamma upon stimulation with tumor cells. T cells cultured after a single exposure to tumor are even more active against pulmonary tumor than T cells cultured from mice immunized repeatedly. This culture system can rapidly induce T cell proliferation and differentiation into mature effector cells, and the resulting cells demonstrate an enhanced ability to treat visceral metastases, but a decreased ability to treat subcutaneous tumor. Thus T cells cultured after a single exposure to tumor represent an ideal population of cells for use in human adoptive immunotherapy trials.

Animals↗

PubMed1996

Efficacy of in vitro sensitized cells generated by in vivo priming with OK-432 for adoptive immunotherapy of the poorly immunogenic B16-Bl6 melanoma.

We investigated the efficacy of the streptococcal preparation OK-432 as an adjuvant for in vivo priming in induction of sensitized cells for adoptive immunotherapy of the poorly immunogenic B16-BL6 (BL6) melanoma. C57BL/6 (B6) mice were immunized subcutaneously (s.c.) with 3 x 10(6) viable BL6 tumor cells admixed with various doses of OK-432 ranging from 1 to 100 micrograms in the foot-pad. Draining popliteal lymph nodes (LNs) were harvested 7 days after immunization and LN cells were further sensitized with irradiated tumor cells in the presence of 60-300 IU/ml of IL-2 for 11 days. These in vitro sensitized (IVS) cells (2 x 10(6)) were transferred intravenously (i.v.) to B6 mice bearing 4-day pulmonary metastases established by i.v. injection of 2-4 x 10(5) viable BL6 cells. The mice were also received intraperitoneally (i.p.) 4 x 10(4) IU/day of IL-2 for 4 days after adoptive transfer. Transfer of IVS cells from mice immunized by s.c. injection of tumor cells admixed with 10 micrograms of OK-432 significantly reduced the numbers of BL6 pulmonary metastases compared with that of control IVS' cells without the administration of OK-432 (P = 0.003). These effective IVS cells also significantly prolonged the survival of treated animals (P = 0.003). Functional IVS cells required in vitro stimulation with tumor cells. However, addition of OK-432 in the vaccine resulted in no enhancement of in vitro cytotoxicity and no characteristic change of phenotype of IVS cells. These results suggest that in vivo priming of OK-432 facilitates the sensitization of tumor-reactive T-cells. The procedure of in vivo priming with OK-432 may be beneficial in the adoptive immunotherapy of melanoma.

Animals↗

PubMed1996

Current status of adoptive immunotherapy of cancer.

The sentinel observations made by William B. Coley. M.D. in the 1890s that patients with malignancics can respond to the intratumoral inoculation of live bacterial organisms or bacterial toxins became the cornerstone for the development of immunotherapy for cancers. It has been repeatedly demonstrated that tumors express unique proteins which can trigger an immune response. The adoptive transfer of immune cells to the host with established malignancy can mediate complete eradication of local or disseminated tumors and result in systemic immunity. This review summarizes the current experimental as well as clinical status of adoptive immunotherapy of cancer. There are a number of different methods to isolate tumor-reactive T cells from the tumor-bearing host and allow for their ex vivo expansion. A new direction in this field includes attempts to up-regulate the immunogenicity of tumors by genetically modifying tumor cells to express immunoregulatory peptides (i.e. cytokines, co-stimulatory molecules, etc.) in order to exploit endogenously weak immune responses to autochthonous tumors. Other new directions involve developing methods to generate or isolate tumor-reactive T cells subsets by selective in vitro stimulation (i.e. bacterial superantigens) or genetic engineering of activated T cells to enhance their ability to mediate tumor destruction. Although adoptive immunotherapy has thus far added little to the routine treatment of human cancer, it is likely that continued efforts at defining the elements involved in T cell recognition and destruction of tumor cells will broaden the applicability of T cells as important therapeutic reagents.

Clinical Trials as Topic↗