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Biomedical subjects

G Parmiani

Publications and source records attributed to G Parmiani.

At least 289 records · Page 16Linked to original sources
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Adoptive immunotherapy of cancer with immune and activated lymphocytes: experimental and clinical studies.

Recent studies of passive adoptive immunotherapy of experimental tumors indicate that histologically different neoplasms can be cured by this procedure in mice, rats and guinea pigs. In this paper two main approaches of adoptive immunotherapy with lymphocytes are considered. One which makes use of specific tumor-immune cells and is applicable to immunogenic tumors, and the other which uses activated (allostimulated and/or IL-2-activated) lymphocytes and is applicable to immunogenic and non-immunogenic neoplasms. Experimental models of both approaches and results provided by them are reviewed. These studies indicate that transfer of tumor-reactive lymphocytes with or without the combined administration of IL-2 into syngeneic tumor-bearing animals can lead to the eradication of a disseminated neoplasia when certain conditions are met. In particular, it was found that high tumor burdens, delay of treatment and low number of transferred lymphocytes can adversely affect the results. It has also been shown that the therapeutic effect of treatment with anti-cancer drugs or irradiation may be significantly improved by the addition of adoptive immunotherapy. The successful treatment of immunogenic tumors often requires the inhibition of suppressor lymphocytes by Cy or irradiation. Non-immunogenic tumors can be successfully treated only by providing activated lymphocytes and high doses of IL-2. Recent findings of few available human studies of adoptive immunotherapy are also reviewed, and the problems of toxicity and possible therapeutic effects of infusion of autologous, activated lymphocytes and IL-2 are discussed.

Animals↗
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The undefined relationship between tumor antigens and histocompatibility antigens on cancer cells.

The data pertaining to the possible relationship between histocompatibility antigens (HA) and tumor-specific transplantation or tumor surface antigen (TSTA or TSA) are reviewed. The HA profiles of certain experimental and human neoplasms have been found to be altered either from the quantitative (increased expression of some antigenic specificities and decreased expression or even lack of other HA) or qualitative point of view (appearance of alien, genetically inappropriate HA). The authors entertain the possibility that the persence of TSTA or TSA on cancer cells may be linked to alterations of the HA profile. Evidence in favour of the idea that tumor antigens may actually to alien MHC products, alien minor HA or modified HA, is reviewed. Findings on structural relationships between TSA and beta2-microglobulin are also summarized. In the authors' opinion, no definitive conclusions can be reached at the present time on the relationship between TSTA or TSA and HA of cancer cells.

Animals↗
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Two autologous melanoma-specific and MHC-restricted human T cell clones with identical intra-tumour reactivity do not share the same TCR V alpha and V beta gene families.

Among tumour infiltrating lymphocytes (TIL) of a melanoma patient, A CD8+, WT31+ CTL clone (8B3) had been previously isolated which exhibited specific and MHC-restricted lytic activity against the autologous tumour. To molecularly characterize T cell receptor (TCR) alpha and beta transcripts of clone 8B3, sequence analysis of several cDNA isolates was carried out. Such analysis indicated that the functional alpha and beta chain of 8B3 are composed of V alpha 2.1/J alpha/C alpha and V beta 8.2/D beta/J beta 1.2/C beta 1 gene segments. Eleven additional melanoma-reactive T cell clones from the same patient (one MHC-restricted and 10 MHC-unrestricted) were analysed for usage of the 8B3 V alpha 2 and V beta 8 gene segments by Northern blot hybridization. Neither the V alpha 2 nor the V beta 8 segments were used by 8D9, the second MHC-restricted melanoma-specific TIL clone that displayed intra-tumour reactivity identical to that of 8B3 recognizing only 4 out of 25 melanoma clones isolated from the same metastases. No V beta 8 expression was found among the MHC-unrestricted T cell clones and all but two (found in duplicate as 4C4 and 4A6) were also negative for V alpha 2 expression. Southern blot analysis revealed different TCR beta chain rearrangements in most MHC-unrestricted T cell clones providing evidence of their independent derivation. Taken together these findings show that TCR of clone 8B3 is unique in composition and not shared by MHC-unrestricted melanoma-reactive T cell clones. The different set of V alpha and V beta families used by clone 8D9 further indicates that the TCR usage in the specific and MHC-restricted response to melanoma can be polyclonal.

Amino Acid Sequence↗
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Phenotypic heterogeneity of HLA products on human melanoma cells.

The expression of class I and class II HLA antigens has been studied on primary and metastatic human melanomas, and on cell clones derived from the latter. A panel of monoclonal antibodies and flow cytofluorometric analysis were used to evaluate the presence of HLA-A, B, C and -DR, DQ antigens on freshly isolated tumour cells. HLA class I antigens were present on 91% and 93% of primary and metastatic tumours, respectively. Sixty per cent of primary and 50% of metastatic melanomas expressed HLA-DR antigens, whereas 38% and 21% of cases were positive for HLA-DQ. A marked heterogeneity was evident among primary and metastatic lesions for expression of class I and II antigens. Similar findings were obtained by analysing the phenotype of melanoma clones which indicates that a marked antigenic heterogeneity for class I and II HLA antigens occurs even among clones isolated from short-term cultures of metastatic melanomas.

Antibodies, Monoclonal↗
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Loss of polymorphic restriction fragments of class I and class II MHC genes in a malignant melanoma.

DNAs from human malignant melanoma cells and autologous peripheral blood lymphocytes were evaluated by Southern blot analysis with probes for class I and II HLA genes. DNA of melanoma cells digested with PvuII, EcoRI and BglI and hybridized with a DR beta probe showed a loss of several fragments when compared with DNA from lymphocytes. The same DNAs were not distinguishable when hybridized with a DQ beta probe. Analysis of melanoma and autologous lymphocyte DNAs from the same patient with a class I cDNA, after digestion with several endonucleases, revealed a further loss of fragments in melanoma cells. Comparison of restriction fragment patterns of melanoma and lymphocytes with those of homozygous, serologically-typed cell lines indicated that melanoma cells have lost fragments diagnostic of DR2 and A1 antigens. A densitometric analysis of signals of several oncogenes in comparison with that of DR indicated that a duplication of the remaining DR allele had occurred in melanoma cells.

DNA, Neoplasm↗
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Syngeneic antitumor and antiembryo immunization affecting pregnancy in mice.

Groups of virgin BALB/c female were immunized against methylcholanthrene, SV40-induced or spontaneous syngeneic sarcoma cells or against syngeneic mitomycin-C blocked embryonic cells. Females were then mated to syngeneic males and observed for pregnancy rate and size of litters. To mimic the antiembryo immunization occurring during normal pregnancy, other experimental groups were added in which midgestational embryo fragments were kept in cell-impermeable diffusion chambers placed in the peritoneal cavity of virgin femals for 20 days, and removed before mating these females with syngeneic males. In all cases, antitumor and antiembryo immunization significantly reduced the number of successful pregnancies after the 1st mating while the second pregnancy appeared to be unaffected by the treatment. A significant reduction in the mean litter size was found, in mice immunized with embryonic tissues or with the SV40-induced sarcoma but not in those immunized with methylcholanthrene-induced or spontaneous tumors.

Animals↗
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Immunogenic neoplastic clones derived in vitro from an originally non-immunogenic BALB/c fibrosarcoma.

A non-immunogenic fibrosarcoma (SDC2), obtained by spontaneous neoplastic transformation of BALB/c fibroblasts cultured within a diffusion chamber kept in the peritoneal cavity of (BALB/c x C3Hf)F1 mice, was maintained in tissue culture for 10 passages. Three different clones were then derived from the in vitro neoplastic population. Each of the clones, the original in vivo tumor, and its in vitro line taken at the 10th passage (before cloning) were tested for the presence of individual tumor-associated tramsplantation antigens (TATA) by in vivo growth and excision assay. Contrary to the original SDC2 neoplasm, its in vitro line and 2 out of 3 clones (CL1-SDC2 and CL3-SDC2) were immunogenic, whereas the other clone (CL6-SDC2) displayed no immunogenicity. In addition, CL1-SDC2 and CL3-SDC2 were able to induce a reciprocal cross-protection in in vivo transplantation tests, thus showing common TATA; no cross-reactions were found between these clones and 2 other chemically-induced immunogenic sarcomas. The results suggest an antigenic heterogeneity in the original population of the nonimmunogenic SDC2 sarcoma, with the presence of antigenic but sub-immunogenic neoplastic cells.

Animals↗