Effect of chemotherapy and immunotherapy on tumor-specific immunity in melanoma.

Abstract

A B S T R A C T The effects of chemotherapy, with nitrosoureas or dimethyl-triazeno-imidazole-carboxamide (DTIC), or immunotherapy with Bacillus Calmette-Guerin (BCG), on cell-mediated immunity (CMI), and serum blocking factor (BF) to melanoma cells were studied in 23 patients. Studies were performed with autologous or allogenic melanoma target cells obtained from recent biopsy, in 16 mm diameter plastic wells. Assays for lymphocyte-mediated cytotoxicity and BF were performed at weekly intervals over the course of3-4 mo, with some studies extending beyond 3 yr. The specificity of cytotoxicity was good with these methods. Nine patients given nitrosoureas, predominantly methyl-chloroethyl-cyclohexylnitrosourea, showed a transient decline in CMI from 42.2 to 14% 3 wk after administration of a single dose of the agent, with a rapid recovery within 1 wk. 10 patients given 5-day courses of DTIC at 3-wk intervals showed no decline in CMI after two courses, and 7 of the 10 had no decline even after three courses. Three of the four patients who achieved a remission lost BF previously present; BF reappeared in both patients studied during a subsequent relapse. BCG intradermally or intralesionally elevated CMI within 2 mo after initiation of therapy, but despite continuation of the injections CMI returned to base line in all but two of the nine patients studied. These results indicate that chemotherapy for melanoma with nitrosoureas

In vitro antitumor reactivity of mononuclear leukocytes from cancer patients receiving immunotherapy with BCG

“…There is evidence to suggest that potentiation of cell-mediated cytotoxicity by serum occurs at the level of the target cells and is mediated by antitumor antibodies [25], whereas blocking effect at the target cell level is probably mediated by antigen-antibody complexes ing BCG administration has been reported in some patients with melanoma [27-301, but not in others [31]. Decline in MCMC has also been noted by other investigators [28,29].…”

A phase III comparison of methyl-CCNU + vincristine with or without BCG + allogeneic tumor cells in metastatic melanoma

“…Methyl-235 C C N U is more immunosuppressive than DTIC and could have interfered with the immunotherapy [2,9]. However, methyl-CCNU did not prevent 12/14 PPDnegative patients from converting to PPD-positive following chemoimmunotherapy.…”

Chemotherapy for Melanoma: The Resultant of Conflicting Vectors

“…11 If the immune response to the tumor is blunted, an undesirable activity of the drug has occurred, and could cause the tumor to behave more aggressively. 15 This relative lack of immunosuppressive potency may serve as a countervailing force against the in vivo induction of tumorigenic or angiogenic cytokines found by Lev et al On the other hand, the hydroxy-congener doxorubicin had strong antitumor activity accompanied by little immunosuppression.…”

“…As a class, the alkylating agents are among the most immunosuppressive of all. 15 While the in vitro methods used in the late 1970s were undoubtedly inferior to more modern, sensitive in vitro tests of cell-mediated immunity (such as ELISPOT assays for cytolytic T cells), there was a clear difference between the profound, though transient, decline in circulating cytolytic T cells caused by the nitrosoureas, and the inability of DTIC to cause any discernible change. In mice, Spreafico 12 showed that daunorubicin was immunosuppressive but had potent antitumor cytotoxic activity.…”