lipid-a and Carcinoma--Non-Small-Cell-Lung

Fifty-seven patients with MAGE-3-positive measurable metastatic cancer, most of them with melanoma, were vaccinated with escalating doses of a recombinant MAGE-3 protein combined with a fixed dose of the immunological adjuvant SBAS-2, which contained MPL and QS21. The immunisation schedule included 4 intramuscular (i.m.) injections at 3-week intervals. Patients whose tumour stabilised or regressed after 4 vaccinations received 2 additional vaccinations at 6-week intervals. The vaccine was generally well tolerated. Among the 33 melanoma patients who were evaluable for tumour response, we observed 2 partial responses, 2 mixed responses and 1 stabilisation. Time to progression in these 5 patients varied from 4 to 29 months. In addition, a partial response lasting 10 months was observed in 1 of the 3 metastatic bladder cancer patients included. None of the tumour responses described above involved visceral metastases. Immunological responses to the vaccine will be reported separately.

Topics: Adjuvants, Immunologic; Adult; Aged; Antigens, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Cancer Vaccines; Carcinoma, Non-Small-Cell Lung; Carcinoma, Transitional Cell; Female; Humans; Immunization; Lipid A; Lung Neoplasms; Male; Melanoma; Middle Aged; Neoplasm Metastasis; Neoplasm Proteins; Neoplasms; Recombinant Proteins; Saponins; Skin Neoplasms; Survival Analysis; Treatment Outcome; Urinary Bladder Neoplasms

MAGE-3 is the most commonly expressed cancer testis Ag and thus represents a prime target for cancer vaccines, despite infrequent natural occurrence of MAGE-3-specific immune responses in vivo. We report in this study the successful induction of Ab, CD8(+), and CD4(+) T cells in nonsmall cell lung cancer patients vaccinated with MAGE-3 recombinant protein. Two cohorts were analyzed: one receiving MAGE-3 protein alone, and one receiving MAGE-3 protein with adjuvant AS02B. Of nine patients in the first cohort, three developed marginal Ab titers and another one had a CD8(+) T cell response to HLA-A2-restricted peptide MAGE-3 271-279. In contrast, of eight patients from the second cohort vaccinated with MAGE-3 protein and adjuvant, seven developed high-titered Abs to MAGE-3, and four had a strong concomitant CD4(+) T cell response to HLA-DP4-restricted peptide 243-258. One patient simultaneously developed CD8(+) T cells to HLA-A1-restricted peptide 168-176. The novel monitoring methodology used in this MAGE-3 study establishes that protein vaccination induces clear CD4(+) T cell responses that correlate with Ab production. This development provides the framework for further evaluating integrated immune responses in vaccine settings and for optimizing these responses for clinical benefit.

Topics: Adjuvants, Immunologic; Amino Acid Sequence; Antibodies, Neoplasm; Antigens, Neoplasm; Cancer Vaccines; Carcinoma, Non-Small-Cell Lung; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cytokines; Epitopes, T-Lymphocyte; Humans; Lipid A; Lung Neoplasms; Lymphocyte Activation; Melanoma; Molecular Sequence Data; Neoplasm Proteins; Saponins; Th1 Cells; Th2 Cells; Vaccines, Combined; Vaccines, DNA