Immunoselection in vivo: Independent loss of MHC class I and melanocyte differentiation antigen expression in metastatic melanoma

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

“…22 In another study, a comparative analysis of repeated biopsies of the same metastatic lesions over a 9-month period showed a gradual loss of MART-1/ MelanA expression in 4 of 5 patients with tumor progression. 23 Thus, it would appear that the use of antibodies to MAA for diagnostic purposes would possibly be compromised in patients participating in these protocols.…”

Immunology and immunotherapy approaches for prostate cancer

“…50 However, the majority of these clinical trials were performed in melanoma patients using TAA-based vaccinations. Vaccine-induced T-cell responses were detected in melanoma patients without reporting any clinical responses in some trials, 51,52 whereas clinical responses including stabilization of disease, partial and even complete tumour regression were reported in other trials. [53][54][55][56][57] Although most immunotherapy studies have been performed in melanoma patients, the discovery of antigens on other tumours and the principles gained from melanoma patients can lead to the expansion of these studies to patients with more common tumours.…”

“…86 Determination of the ability of CD8 þ CTL to kill tumours using cytotoxicity assays is an important indicator for the in vivo antitumour activity. Such ability is measured by the traditional 51 Cr-release assay, or alternatively by using some flow cytometric methods based on labelling targets with membrane dye and measuring any cell death within the target population by a viability dye. [87][88][89] Cytokine secretion from T cells in response to antigen stimulation may be detected by measuring either bulk cytokine production using an enzyme-linked immunosorbent assay or multiplexed flow cytometric assays, 90 whereas cytokine assay at single-cell level can be performed by the enzyme-linked immunospot (ELI-SPOT) assay.…”

Developing effective cancer vaccines: design and monitoring are critical

“…An additional concern with the use of minimal epitope vaccines is the increased potential for immune selection of tumours with subtle genetic variations that no longer express the peptide epitope(s). Immunohistochemical analysis of repeat biopsies from patients with metastatic melanoma who had initially responded to a peptide vaccine, but who relapsed despite the presence of peptide-specific cytotoxic T cells, revealed gradual loss of antigen expression in association with disease progression (Jager et al, 1997). Use of vaccines containing one or more whole antigens should induce a polyclonal immune response capable of recognizing multiple antigenic determinants and may prevent tumour escape.…”