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D L Morton

Publications and source records attributed to D L Morton.

At least 91 records · Page 5Linked to original sources
PubMed1998

Assessment of messenger RNA of beta 1-->4-N-acetylgalactosaminyl-transferase as a molecular marker for metastatic melanoma.

Gangliosides GM2 [GalNAc beta 1-4(NeuAc alpha 2-3)Gal beta 1-4Glc beta 1-1Cer] and GD2 [GalNAc beta 1-4(NeuAc alpha 2-8NeuAc alpha 2-3)Gal beta 1-4Glc beta 1-1Cer] are cell surface tumor-associated antigens and have been demonstrated to be important markers of human malignant melanoma progression. Expression of these glycolipid antigens on melanoma tissues can be assessed by immunohistochemistry or biochemical analysis. These methodologies, however, are not logistically practical or sensitive for testing metastatic melanoma cells in blood or in tissue biopsies. In the present study, we hypothesized that the enzyme involved in GM2 and GD2 synthesis, beta 1-->4-N-acetylgalactosaminyltransferase (beta 1-->4GalNac-T), can be a useful marker for detection of occult metastatic melanoma. A reverse transcription PCR and Southern blot assay to detect beta 1-->4GalNac-T mRNA expression was developed. Beta 1-->4GalNac-T mRNA was detected in all 13 melanoma cell lines tested. Metastatic melanoma of lymph nodes and different organ sites expressed beta 1-->4GalNac-T mRNA at various levels. Detection sensitivity of the reverse transcription PCR assay was 1 ng of total RNA extracted from tumor specimens and approximately 5 melanoma cells in 20 million normal donor peripheral blood lymphocytes. In assessment of blood from 126 melanoma patients, beta 1-->4GalNac-T mRNA was more frequently found in advanced-stage melanomas and in patients showing more aggressive tumor progression. Normal donor blood samples (n = 37) were all negative for beta 1-->4GalNac-T mRNA expression. These results suggest that beta 1-->4GalNac-T mRNA is a promising molecular marker for detecting melanoma cells, characterizing antigen expression, and monitoring tumor progression.

Antigens, Neoplasm↗
PubMed1998

Kinetics of three lymphoscintigraphic agents in patients with cutaneous melanoma.

UNLABELLED: Although lymphoscintigraphy is commonly used for the preoperative evaluation of patients with cutaneous melanoma and for intraoperative identification of sentinel lymph nodes, there is no consensus regarding the most useful radiopharmaceuticals or imaging times. METHODS: Fifty-one consecutive patients with clinical American Joint Committee on Cancer Stage I or II melanoma were assigned to one of three groups of 17 for lymphoscintigraphy with one of three radiopharmaceuticals: 99mTc-albumin colloid (AC), 99mTc-human serum albumin (HSA) or 99mTc-sulfur colloid (SC). Colloidal agents were filtered through 0.2 microm filters. After injecting 18.5-30 MBq (500-800 microCi) of the radiopharmaceutical, dynamic monitoring over injection sites and node basins was performed to identify draining lymphatic channels and sentinel nodes. In addition, static digital and analog images were acquired from the injection site and draining node basins immediately after injection and at 30 min (early) and 2 to 4 hr (delayed) after injection. Dynamic and static images were analyzed to determine transit times to the sentinel node, the number of nodes visualized in early and delayed images, the quality of lymph node and lymph channel visualization, the sentinel-to-nonsentinel uptake ratios and the washout rates from injection sites. RESULTS: Early images with all three agents provided reliable identification of sentinel lymph nodes. Technetium-99m-HSA demonstrated faster washout rates from injection sites and better definition of lymph channels than either particulate agent, whereas particulate agents were retained longer in nodes and demonstrated more nodes in delayed images than in early images. All agents demonstrated lymph channels better in early images than in delayed images. In general, variations between patients exceeded differences between agents. Sentinel nodes could not be distinguished reliably from nonsentinel nodes in delayed images alone. CONCLUSION: All three agents are acceptable for cutaneous lymphoscintigraphy, but reliable identification of sentinel nodes and their afferent lymph channels requires early imaging. Delayed imaging or localization alone is unreliable and may lead to incorrect identification of the sentinel node.

Female↗
PubMed1998

Active immunotherapy with allogeneic tumor cell vaccines: present status.

This review will concentrate on allogeneic vaccines for melanoma The important principles of melanoma vaccine effectiveness are discussed in detail, followed by a review of the progress of several clinical trials investigating allogeneic vaccines. No therapeutic cancer vaccine has yet been approved for general use by the US Food and Drug Administration. However, much progress has been made in the field of vaccine immunotherapy, especially for the treatment of melanoma. Active immunotherapy with tumor vaccines is progressing rapidly as an emerging option for cancer therapy.

Antigens, Neoplasm↗
PubMed1997

Recognition of gp43 tumor-associated antigen peptide by both HLA-A2 restricted CTL lines and antibodies from melanoma patients.

Previously, we detected a 43-kDa tumor-associated antigen (TAA) using the human monoclonal antibody L92, which recognizes the tetramer peptide KYQI. In the present study, cell lines of cytotoxic T lymphocytes (CTL) specific to the gp43 peptide (DLTMKYQIF) were established from peripheral blood lymphocytes (PBL) of melanoma patients. Patients' PBL (n = 326) of different HLA Class I types were assessed for gp43 CTL activity. CTL specific to gp43 peptide were generated only from HLA-A2 melanoma patients and not normal donors. gp43 CTL recognized gp43 peptide-pulsed autologous BLC and T2 HLA-A2 target cell lines. Furthermore, CTL lines were shown to kill both HLA-A2 autologous and HLA-A2 allogeneic melanoma cell lines, indicating that gp43 peptide can be processed endogenously and presented by melanoma cells as a common TAA. The gp43 CTL lines did not kill normal cells. Specific amino acids of the peptide were shown to be important determinants in stimulation and recognition of CTL. gp43 peptide, recognized by both antibodies and T cells of melanoma patients, is a novel TAA peptide that may play an important role in anti-tumor immunity in human.

Amino Acid Sequence↗
PubMed1997

Endothelial-selectin ligands sialyl Lewis(x) and sialyl Lewis(a) are differentiation antigens immunogenic in human melanoma.

BACKGROUND: Sialyl Lewis(x) (sLe(x)) and sialyl Lewis(a) (sLe(a)), the endothelial-selectin ligands involved in extravasation of neutrophils and carcinomas, have been identified in human melanoma. This study explored the following issue: If these ligands are immunogenic tumor-differentiation antigens, they would be potential targets for immunotherapy because of their putative roles in extravasation and metastasis. METHODS: Using a cell-suspension enzyme-linked immunosorbent assay (ELISA), the expression of sLe(x) and sLe(a) on the surface of normal melanocytes, melanoma cells from biopsies, and cell lines (M10-v, M24, and M101) constituting melanoma cell vaccine (MCV) were quantitated. Melanoma patients were immunized with the MCV expressing these antigens. Sera of normal individuals, sera of patients, and sera that adsorbed to sLe(x) and sLe(a) were titrated for anti-sLe antibodies by ELISA to verify the immunogenicity of the ligands. RESULTS: The normal melanocytes did not express sLe(x) and poorly expressed sLe(a). Melanoma cells from tumor biopsies and MCV lines expressed both sLe(x) and sLe(a). Sialyl Le(x) was associated with glycoprotein(s) in M10-v, and sLe(a) occurred as a glycolipid moiety in M24. MCV recipients developed high titers for immunoglobulin (Ig)M but not IgG to both ligands. IgM titers to these ligands were low in normal subjects. In some of the preimmune sera of patients, the titers were threefold above normal. Six of 13 MCV recipients developed at least a twofold increase in anti-sLe titers above preimmune level after the second or third immunization. Adsorption studies suggested that both ligands were immunogenic. CONCLUSIONS: The melanoma-associated sLe(x) and sLe(a) are immunogenic neoplasm-differentiation antigens and are therefore potential targets for passive and active specific immunotherapy in the treatment of melanoma.

Animals↗
PubMed1997

Melanoma-associated antigens as messenger RNA detection markers for melanoma.

Melanoma is heterogeneous for its biological properties and melanoma-associated antigens (MAAs). This diversity is partially observed in the expression of the MAAs involved with the melanin synthesis pathway. We therefore developed a sensitive multimarker reverse transcription-PCR plus Southern blot assay using five MAAs as molecular markers to detect primary and metastatic melanoma cells. Melanoma cell lines, melanocytes (cultured), primary and metastatic malignant melanoma tissues, and blood from patients with American Joint Committee on Cancer stage I-IV melanoma were assessed for tyrosinase, tyrosinase-related proteins 1 and 2, Pmel 17, and MART-1/Melan-A. All of the MAA mRNA markers were expressed in 100% of melanoma cell lines and cultured melanocytes, 74% of primary and metastatic tumors (excluding tumor-draining lymph nodes), 43% of tumor-involved lymph nodes, and 43% of patients' bloods. Hypomelanotic melanoma tissues expressed a lower frequency of individual mRNA markers. Overall, at least one mRNA marker was expressed in more than 86% of specimens assayed. Normal tissue specimens from patients and blood from normal volunteer donors were negative for MAA mRNA expression. The multimarker MAA reverse transcription-PCR plus Southern blot analysis was more reliable and sensitive than a single-molecular marker assay for the detection of melanoma cells. This molecular assay can also provide information on MAA mRNA expression of metastatic melanoma cells that may assist in monitoring the therapeutic efficacy of active specific immunotherapy toward specific MAA-bearing melanomas.

Antigens, Neoplasm↗
PubMed1997

Update on active specific immunotherapy with melanoma vaccines.

Although a randomized clinical trial has yet to show a statistically significant improvement in the survival of patients receiving vaccine therapy for malignant melanoma, several studies have shown enhanced survival of patients developing an immune response to a melanoma vaccine. The knowledge and techniques of modern molecular biology and immunology suggest multiple strategies to augment this response. The challenge of immunotherapy research is to determine which combination of approaches leads to a favorable clinical response and how to monitor that response effectively. This review identifies components of a successful vaccine, discusses new ways to modulate and stimulate the immune system, and summarizes some of the more interesting clinical trials of melanoma vaccine immunotherapy.

Adjuvants, Immunologic↗
PubMed1997

Sentinel lymphadenectomy for patients with clinical stage I melanoma.

Consistent results with SLND can only be obtained through the combined efforts of the nuclear medicine physician, the surgeon, and the pathologist. These individuals must have experience with the technical details of SLND and must understand and accept the multidisciplinary nature of this technique. The reports in this issue of the Journal of Surgical Oncology prove that SLND is accurate and reproducible. Drs. Thompson and Karakousis both report a 93% rate of sentinel node identification, and Dr. Reintgen reports a rate of 96%. At JWCI, our overall rate of sentinel node identification has now reached 98%. The ultimate results of SLND as a therapeutic procedure in patients with clinical stage I cutaneous melanoma await completion of our international phase III multicenter trial ("A Clinical Study of Wide Excision Alone Versus Wide Excision with Intraoperative Lymphatic Mapping and Selective Lymph Node Dissection in the Treatment of Patients with Cutaneous Invasive Melanoma"; D.L. Morton, Principal Investigator), which is now in its third year of accrual. At the present time, we believe that lymphatic mapping and selective (sentinel) lymph node dissection is an investigational procedure whose therapeutic utility is unproven. Until clinical trials are completed and there is technique standardization among various centers, this procedure should not be used as routine therapy in a community hospital outside the setting of a clinical trial. Although intraoperative lymphatic mapping and SLND may provide prognostic information, if its therapeutic utility is not demonstrated by current multicenter clinical trials, it is likely to be replaced by molecular RT-PCR techniques that directly measure tumor burden in the blood [21].

Humans↗
PubMed1997

Metastasis of primary melanoma to two separate lymph node basins: prognostic significance.

BACKGROUND AND METHODS: Depending on the location of the primary lesion, melanoma patients may develop metastases in more than one regional lymph node basin. To determine whether this is prognostically significant, we reviewed our experience with melanoma patients who had undergone regional lymphadenectomy (RLND) in two separate basins. RESULTS: Of 3,603 patients who underwent RLND between April 1971 and January 1993, 406 underwent procedures in two separate basins; of these, 120 (30%) had metastases in both basins and 124 (30%) had metastases in one basin. When calculated from the first positive RLND, 1-year, 3-year, and 5-year survival rates were 82%, 48%, and 33%, respectively, for patients with dual-basin involvement and 88%, 59%, and 48%, respectively, for patients with single-basin involvement (p = 0.0173). Median survival from the first positive RLND was 33.5 months for dual-basin involvement and 56.6 months for single-basin involvement. Univariate analysis demonstrated that Breslow thickness of the primary melanoma, clinical status of the regional lymph nodes, number of positive RLNDs, and tumor burden (total number of positive lymph nodes) were significant indicators of survival. The patient's age and gender, the anatomic location and Clark level of the primary melanoma, the disease-free interval before regional metastasis, and the site and timing of RLNDs were not significant by univariate analysis. Multivariate analysis demonstrated significance for Breslow thickness, number of positive RLNDs, and tumor burden. CONCLUSIONS: The survival rate of melanoma patients with regional metastases in two lymph node basins is lower than that of patients with an equal tumor burden confined to a single basin. This suggests that primary melanomas metastasizing to more than one lymph node basin may have a higher metastatic potential, or that dual-basin involvement may increase the risk of systemic spread. We advocate lymphatic mapping, sentinel node biopsy, and selective lymphadenectomy as a cost-effective technique with little morbidity to identify and manage occult metastases in patients who have two lymph basins at risk.

Adult↗
PubMed1997

Cellular cancer vaccine induces delayed-type hypersensitivity reaction and augments antibody response to tumor-associated carbohydrate antigens (sialyl Le(a), sialyl Le(x), GD3 and GM2) better than soluble lysate cancer vaccine.

Allogenic whole cell and lysate cancer vaccines are associated with very different clinical outcome, which could be due to different immune responses to critical tumor-associated antigens. We used a guinea pig model to evaluate the immune responses to melanoma-associated carbohydrate antigens administered in whole cell and soluble lysate vaccines produced from the same cell lines and administered with or without Bacille Calmette-Guerin (BCG). Animals immunized with whole cell vaccine developed a significantly higher delayed-type hypersensitivity (DTH) reaction. The IgG response to all tumor-associated carbohydrate antigens except GD2 was significantly higher in animals immunized with whole cell vaccine than lysate vaccine. This study indicates that whole cell vaccine is superior to soluble or lysate vaccine because it induces a better immune response against cell-surface antigens. The addition of BCG significantly increased the antibody response, suggesting that an exogenous adjuvant may immunopotentiate antigens better in the presence of an intact cell membrane.

Adjuvants, Immunologic↗
PubMed1997

Molecular detection of tumor-associated antigens shared by human cutaneous melanomas and gliomas.

Both melanocytes and glial cells are derived embryologically from the neural ectoderm. Their malignant transformed counterparts, melanoma and glioma cells, respectively, may share common antigens. Numerous tumor-associated antigens have been identified in melanomas but only a few a gliomas. Using an established reverse transcriptase polymerase chain reaction plus Southern blot assay, we compared the mRNA expression of melanoma-associated antigens (MAAs) of melanomas to brain tumors primarily derived from glial cells. The MAAs studied included tyrosinase (Tyr), tyrosinase-related protein-1 and -2 (TRP-1 and TRP-2), gp100, human melanoma antigen-encoding genes 1 and 3 (MAGE-1 and MAGE-3), and melanotransferrin (p97). Glioblastoma multiforme (n = 21), anaplastic astrocytoma (n = 3), ependymoma (n = 2), meningioma (n = 3), oligodendroglioma (n = 1), and melanoma (n = 12) tumor specimens were assayed for MAA mRNA expression. Glioblastoma multiforme, astrocytoma, and melanoma cell lines were also assayed. We observed that individual MAA mRNAs were expressed in these brain tumors and cell lines at varying frequencies. The melanogenesis-pathway-related MAAs Tyr, TRP-1, TRP-2, and gp100 mRNAs were also expressed at different levels in normal brain tissues but at a much lower frequency than in glioblastoma multiforme and melanoma. MAGE-1 and MAGE-3 mRNA were expressed in different types of tumor specimens and cell lines but never in normal brain tissue. Tumor antigen p97 was expressed in all types of tumors and also in normal brain tissues. These studies demonstrate that melanomas and primary brain tumors express common MAAs and could be exploited in patients with malignant glioma by active specific immunotherapy against these common MAAs.

Antigens, Neoplasm↗
PubMed1997

Lymphocytes from lymph nodes at different distances from human melanoma vary in their capacity to inhibit/enhance tumor cell growth in vitro.

Eighty-six lymph nodes at measured distances from a primary tumor were removed from 68 patients with malignant melanoma. The ability of lymph-node lymphocytes (LNL) from these nodes to modulate proliferation of a melanoma cell line (UCLA-SO-M14) in vitro was tested. LNL from the majority of lymph nodes (66%) inhibited M14 growth, but LNL from 34% of nodes stimulated growth of the cell line. Peripheral blood mononuclear cells always inhibited M14 growth. Distance of a node from the primary tumor was found to be an important determinant of LNL activity. This was demonstrated using pairs of nodes from individual patients. In 86% of cases, LNL from nodes located nearer to the tumor inhibited M14 growth less than LNL from more distant nodes. Stimulation of M14 growth was commonest with LNL from nodes located near to the tumor. CD8+ T cells were largely responsible for M14 growth inhibition, whereas CD4+ cells were associated with stimulation of M14 growth. Removal of CD4+ lymphocytes from growth stimulatory LNL resulted in a CD4-depleted LNL preparation that inhibited M14 cell proliferation. The environment in lymph nodes located dose to tumors may thus favor growth of metastatic tumor cells.

CD4-Positive T-Lymphocytes↗
PubMed1996

Quantitation of the density of cell surface carbohydrate antigens on cancer cells with a sensitive cell-suspension ELISA.

The density of carbohydrate epitopes on the surface of tumor cells is a governing factor for immune recognition and antibody-mediated targeting of tumor-associated carbohydrate antigens in cancer immunotherapy. A sensitive cell-suspension ELISA (cs-ELISA) is developed for quantitation of the functionally exposed carbohydrate epitopes on the cell surface. The factors affecting the measurement of tumor-cell surface glycoconjugates are evaluated using three human melanoma cell lines before and after exposure to various cell preservation treatments. The results of cs-ELISA are compared with the quantitative profile obtained by biochemical and flow cytometry assays. Cs-ELISA measures the density of the functionally exposed specific sugar epitopes on the surface of tumor cells, even in the presence of other similar carbohydrate antigens, provided that the monoclonal antibodies to carbohydrate epitopes are monospecific and sensitive, and that the cells are viable and present in optimal density. Of the three melanoma cell lines, M10-v and M101 expressed disialolactosyl residues of GD3 at concentrations of 5-6 pmol/10(6) cells and 2-3 pmol/10(6) cells, respectively. In both cell lines, the cell-surface GD2 was less than 1.0 pmol/10(6) cells. M24 melanoma cells expressed trace quantities (< 0.1 pmol/10(6) cells) of GD3 and GD2. Trypsinization of M10-v and M101 cells significantly reduced the cell-surface expression of GD3, suggesting GD3 loss, but increased the expression of GD2, suggesting crypticity of membrane-bound GD2. Cs-ELISA results showed that cryopreservation with 10% DMSO and irradiation at 15 krad decreased melanoma cell viability and ganglioside expression for M10-v but not M101 and M24. Formalinization did not affect cs-ELISA measurement of cell-surface carbohydrates. Cs-ELISA was used to monitor the quantity of incorporation of exogenous GD3 onto the surface of GD3-deficient M24 cells. Cs-ELISA for assessment of density of cell surface carbohydrate epitopes may be useful to characterize different types of tumors, to develop carbohydrate-based whole cell vaccines from tumor biopsies, to monitor the effects of cell preservation treatments commonly used in a whole cell vaccine preparation, and to evaluate the incorporation of a particular glycolipid (antigen or adjuvant) into glycolipid-deficient cells that are useful for carbohydrate-based active specific immunotherapy.

Antibodies, Monoclonal↗
PubMed1996

Interleukin 4 inhibits hepatocyte growth factor-induced invasion and migration of colon carcinomas.

Hepatocyte growth factor (HGF) is known to have a number of biological properties including promoting tumor progression of human carcinomas. Metastasis involves a number of events that are attributed to induction by paracrine factors such as HGF. Identification of natural inhibitors of these events would allow better control of tumor progression. Recently we demonstrated that interleukin 4 (IL-4) can regulate proliferation of various human carcinoma cell lines. In the present study, we used established human colon carcinoma cell lines and primary colon carcinoma cell cultures to determine if IL-4 could regulate HGF-induced cell proliferation and other events of tumor progression such as MMP (matrix metalloproteinases)-1, -2, and -9 production, cell migration and cell-matrix invasive activity. All colon carcinoma cell lines expressed HGF and IL-4 receptors. IL-4 significantly inhibited HGF-induced proliferation of one cell line. Cell-matrix invasion was significantly enhanced by HGF (0.1-10 ng/ml); IL-4 (1-10 U/ml) significantly inhibited HGF-induced invasion in a dose-dependent manner. IL-4 also inhibited HGF-induced cell-matrix invasion of metastatic colon carcinoma cells and HGF-induced cell migration. HGF enhanced MMP-1, -2, and -9 production by cell lines. This effect could be inhibited by IL-4. These findings indicate that IL-4 is a potent inhibitor of HGF-induced invasion and metastasis-related functions of human colon carcinoma cells.

Antigens, CD↗
PubMed1996

Detection of beta-human chorionic gonadotropin mRNA as a marker for cutaneous malignant melanoma.

The beta chain of human chorionic gonadotropin (hCG) hormone is produced by fetal cells, gonadal cell tumors and several types of non-gonadal carcinoma. hCG is composed of an alpha and a beta chain, the latter of which can be used to distinguish the molecule from other related gonadotropin hormones. Detection of beta-hCG mRNA transcripts can be potentially useful as a marker to identify tumor cells. We devised a highly specific and sensitive assay to detect the atavistic expression of beta-hCG in cutaneous melanoma by RT-PCR. Twenty-four melanoma cell lines and 43 melanoma biopsies were evaluated for beta-hCG mRNA expression. An RT-PCR assay was developed to specifically distinguish beta-hCG poly-A mRNA from other related gonadotropin beta chains. This was performed by endonuclease digestion of a unique Sty 1 site in the beta chain, followed by Southern blot analysis with a beta-hCG cDNA probe. Of the 24 melanoma cell lines analyzed, 18 expressed beta-hCG mRNA. Analysis of melanoma biopsy specimens revealed beta-hCG mRNA expression in 17/25 melanoma-positive TDLN, and in only 5/15 non-lymphoid melanoma metastases. Beta-hCG mRNA expression had a 53% correlation to tyrosinase mRNA, a predominant melanoma marker. Beta-hCG mRNA was not detected in normal donor PBL and normal lymph nodes. Detection of beta-hCG mRNA expression may be a useful molecular marker to define a subset of malignant melanoma.

Base Sequence↗
PubMed1996

Surgical resection for melanoma metastatic to the gastrointestinal tract.

OBJECTIVE: To evaluate the role of surgery in the survival of patients with melanoma metastatic to the gastrointestinal (GI) tract. DESIGN: Retrospective review. SETTING: Tertiary cancer center. PATIENTS: One hundred twenty-four potential surgical candidates with metastatic melanoma in the stomach, small intestine, colon, or rectum. MAIN OUTCOME MEASURES: Operative morbidity and mortality, relief of presenting symptoms, and median and 5-year survival. RESULTS: The median disease-free interval prior to diagnosis of GI tract metastasis was 23.2 months (range, 1-154 months). Patients typically presented with crampy abdominal pain, symptomatic mass, and/or occult GI tract blood loss. Of the 124 patients, 69(55%) underwent surgical exploration of the abdomen, 46 (66%) had curative resection, and 23 (34%) had a palliative procedure. There was only 1 operative death and 1 major operative complication; 67 (97%) of 69 surgical patients experienced postoperative relief of their presenting GI tract symptoms. The median survival in patients undergoing curative resection was 48.9 months, compared with only 5.4 months and 5.7 months in those undergoing palliative procedures and nonsurgical interventions, respectively. By multivariate analysis, the 2 most important prognostic factors for long-term survival were complete resection of GI tract metastases and the GI tract as the initial site of distant metastases. CONCLUSIONS: Almost all patients with melanoma and GI tract metastases can have palliation of symptoms by surgical intervention with minimal morbidity and mortality. The high 5-year survival rate associated with complete surgical resection of GI tract metastases indicates that surgery should be strongly considered for this subgroup of patients with melanoma and distant metastatic disease.

Female↗
PubMed1996

Immune response to polyvalent melanoma cell vaccine in AJCC stage III melanoma: an immunologic survival model.

BACKGROUND: Our polyvalent, allogeneic melanoma cell vaccine (MCV) induces immunoglobulin M (IgM) and immunoglobulin G (IgG) class antibodies to a 90-kDa glycoprotein melanoma-associated antigen (MAA). Additionally, MCV induces delayed-type hypersensitivity (DTH) responses that we previously correlated with survival. We hypothesized that early DTH responses to MCV and early humoral responses to the 90-kDa MAA expressed on MCV cells may be predictive of overall survival. We tested this hypothesis by monitoring immunologic profiles in 59 patients with melanoma who were receiving MCV after surgical resection of regional lymph node or soft-tissue metastases. METHODS: Blood was drawn before vaccine administration, biweekly for 6 weeks, and then monthly. DTH to MCV was recorded at 0, 2, 4, and 8 weeks of MCV therapy. Mean antibody titers during the first 6-week interval were calculated. Changes in DTH were calculated as the difference between peak and prevaccine values (delta DTH). RESULTS: At a median follow-up of 75.6 months (range 5-138), univariate analysis assigned prognostic significance to gender (p = 0.046), lymph node involvement (p = 0.024), delta DTH (p = 0.044), mean anti-90-kDa MAA IgG (p = 0.0009), and mean anti-90-kDa MAA IgM (p = 0.0014). In multifactorial analysis, only the three immunologic variables significantly impacted survival (p = 0.046, 0.0005, and 0.0053, respectively). A mathematical model based on delta DTH and mean anti-90-kDa MAA IgG and IgM titers closely approximated the observed individual and overall survival rates. CONCLUSIONS: The correlation between overall survival and initial humoral/cellular immune responses to MCV immunotherapy may be useful in selecting patients most likely to benefit from prolonged adjuvant immunotherapy.

Adolescent↗