ENHANCEMENT OF LOW-DOSE MELPHALAN-INDUCED TUMOR ERADICATING IMMUNITY BY DEPLETION OF CD4+ T-CELLS (MEETING ABSTRACT)

Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.

ENHANCEMENT OF LOW-DOSE MELPHALAN-INDUCED TUMOR ERADICATING IMMUNITY BY DEPLETION OF CD4+ T-CELLS (MEETING ABSTRACT)

FASEB J; 5(6):A1773 1991. Unique Identifier : AIDSLINE ICDB/91676525
Weiskirch LM; Mokyr MB; Univ. of Illinois, Chicago, IL 60612

Abstract: We have previously shown that a low dose (2.5 mg/kg) of melphalan (L-phenylalanine mustard; L-PAM) is curative for approx 90% of BALB/c mice bearing a large sc MOPC-315 tumor and extensive metastases if CD8+ T-cell-dependent antitumor immunity aids in tumor eradication. The CD8+ T-cells were shown to eradicate at least part of the sc tumor nodule through a CTL-type lytic mechanism. Here, we show that CD8+ splenic T-cells from BALB/c mice that are engaged in tumor eradication as a consequence of low-dose L-PAM therapy (L-PAM TuB spleen cells) can, in conjunction with low-dose L-PAM (adoptive chemoimmunotherapy; ACIT), cause the complete regression of a large MOPC-315 tumor in a substantial percentage of T-cell deficient (athymic nude) mice. A drastic improvement in the therapeutic effectiveness of L-PAM TuB spleen cells in ACIT was achieved when the adoptively transferred spleen cells were depleted of CD4+ cells. Interestingly, depletion of CD4+ T-cells from L-PAM TuB spleen cells enhanced the ability of the spleen cells to generate a CTL-type lytic activity against MOPC-315 tumor cells. Finally, depletion of CD4+ T-cells also improved the curative effectiveness of a suboptimal dose of L-PAM (0.75 mg/kg) for BALB/c mice bearing a large MOPC-315 tumor. Thus, the antitumor immunity acquired as a consequence of low-dose L-PAM therapy by MOPC-315 tumor bearers is apparently downregulated by CD4+ T-cells.

Keywords: Animal Cell Line Cytotoxicity, Immunologic/*DRUG EFFECTS/IMMUNOLOGY CD4-Positive T-Lymphocytes/*DRUG EFFECTS/IMMUNOLOGY Dose-Response Relationship, Drug Melphalan/*ADMINISTRATION & DOSAGE Mice Mice, Inbred BALB C Mice, Nude Neoplasm Transplantation Neoplasms, Experimental/*IMMUNOLOGY ABSTRACT
912130
M91C4075

AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted funding from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, Gill Foundation, the National Library of Medicine, Quest Diagnostics, Roche and Trimeris, and donations from users like you. Always watch for outdated information. This article first appeared in 1991. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1991. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .