Development of Cancer Immunotherapies Based on Identification of the Genes Encoding Cancer Regression Antigens

Abstract

Tumor-infiltrating lymphocytes (TILs) have been grown from patients with metastatic melanoma and administered to the autologous patients to identify those TIL populations capable of mediating tumor regression. These TILs have been used to clone the genes that encode melanoma antigens. With the use of this strategy, we have identified six different genes encoding antigens restricted by multiple HLA alleles that appear to be related to tumor regression in patients. These antigens are now being used to develop immunization approaches for the treatment of patients with metastatic melanoma. The availability of genes encoding unique cancer antigens is opening new possibilities for the development of immunotherapies for the treatment of patients with cancer.

Immunizing Patients With Metastatic Melanoma Using Recombinant Adenoviruses Encoding MART-1 or gp100 Melanoma Antigens

“…In recent years, multiple tumor-associated antigens present in human melanomas have been identified and characterized [reviewed in (1,2,33)]. TILs obtained from HLA-A2-positive individuals predominantly recognize the MART-1/MelanA and gp100 nonmutated, melanoma-melanocyte differentiation antigens expressed by the great majority of melanomas and these melanoma-melanocyte differentiation antigens are also expressed on melanocytes but not other normal tissues or other tumors (3)(4)(5)30).…”

“…Assay of anti-MART-1 reactivity in peripheral blood mononuclear cells (PBMCs) from patients immunized with recombinant adenovirus encoding MART-1 or flu peptide (1 μg/mL). † All postimmunization PBMCs were obtained after two injections of adenovirus MART-1 except for patients 4,6, and 9 who were tested after three, one, and four immunizations, respectively, because of availability of PBMCs.…”

Identification of a Novel Human Cancer/Testis Antigen, KM-HN-1, Recognized by Cellular and Humoral Immune Responses

“…Identification of tumor antigens capable of inducing an anticancer immune response in cancer patients and development of immunogenic cancer vaccines targeting these antigens represent formidable tasks confronting tumor immunologists (1). In the early 1990s, van der Bruggen et al (2) and Traversari et al (3) reported the first successful cloning of a human tumor antigen, termed melanoma antigen-1 or MAGE-1 (subsequently renamed MAGE-A1), that elicited a spontaneous CTL response in an autologous melanoma patient.…”

Melanoma antigen expression in serial fine-needle aspiration samples in patients with metastatic malignant melanoma participating in immunotherapy clinical trials

“…Clinical trials using immunodominant peptides from melanoma associated antigens and recombinant adenoviruses coding human MAA for the treatment of patients with melanoma are ongoing at the NCI. [1][2][3][4][5][6][7][8][9] Melanoma antigens associated with HLA-A*0201, 11,12 which include MART-1/Melan A, 13,14 gp100/Pmel 17, 9 tyrosinase, 15 MAGE-3, 16 and N-acetylglucosaminyltransferase V, 17 are shared by most melanoma cells. The T-cell epitopes responsible for recognition of MAA have led to the development of vaccination pro- tocols based on the administration of short peptides representing such epitopes to patients with MMM.…”