Adjuvant MAGE-A3 Immunotherapy in Resected Non–Small-Cell Lung Cancer: Phase II Randomized Study Results

Abstract

In this early development study with a limited number of patients, postoperative MAGE-A3 immunization proved to be feasible with minimal toxicity. These results are being investigated further in a large phase III study.

Assessment of MAGE-A Expression in Resected Non–Small Cell Lung Cancer in Relation to Clinicopathologic Features and Mutational Status of EGFR and KRAS

“…The physiologic function of MAGE-A proteins and their role in cancer have not been elucidated, although there is increasing evidence that some MAGE-A proteins may correlate with poor clinical outcome (11,15). MAGE-A antigens, nonetheless, are immunogenic and are important targets of emerging immunotherapy approaches in NSCLC (16). New therapies using potent immunomodulatory antibodies are being assessed in NSCLC, and have yielded the first evidence of clinical efficacy (17,18).…”

Immune targets and neoantigens for cancer immunotherapy and precision medicine

“…However, clinical studies using high-affinity MART-1 TCR-engineered T cells showed severe toxicity, including the destruction of normal melanocytes in the skin, eye, and ear, and sometimes requiring local steroid administration to treat uveitis and hearing loss [203], compared with patient-derived TCR-engineered T cell therapy [206]. Similarly, serious toxicity was not observed with endogenous MAGE-A3-reactive T cells from cancer patients or patients vaccinated with a MAGE-A3 protein [188,207]. MAGE-A3 is highly expressed in cancer cells, but not in normal cells.…”

“…A multi-center phase II clinical trial using gp100 peptide with or without IL-2 shows that the gp100 peptide vaccine plus IL-2 group had a significant improvement in centrally verified overall clinical response as compared with the IL-2-only group (16% vs 6%), as well as longer progression-free survival [185]. MAGE-A3 peptide/protein vaccines were also tested in phases II and III clinical trials [186][187][188], but a MAGE-A3 phase III clinical trial failed to meet the projected requirement in patients with resected nonsmall cell lung cancer. Consistent with these clinical development of cancer vaccines, phase I trials using NY-ESO-1 recombinant protein or synthetic peptides have been conducted in melanoma and ovarian cancer patients [189][190][191][192], showing that NY-ESO-1 vaccines can induce antigen-specific immune responses, but are insufficient to eradicate cancer cells.…”

Radiotherapy and Immunotherapy Combinations in Non-small Cell Lung Cancer: A Promising Future?

“…Active immunotherapy approaches include non-specific immune modulation (use of interleukin and interferon), therapeutic vaccines (e.g. MAGE-A3 vaccine), modulation of T-cell function and oncolytic viruses and have been slower to demonstrate clinical efficacy [4][5][6]. However, it is the modulation of T-cell function with the immune checkpoint inhibitors which modulate the anti-CTL antigen-4 (CTLA-4) and the antiprogrammed death-1 (PD-1) ligand function which has particularly attracted interest over the last 5 years with durable clinical responses being seen in malignant melanoma, renal cell carcinoma and non-small cell lung cancer, amongst other tumour types [7].…”