Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.
Thymic anti-tumor effectors in mice cured of lymphoma by cyclophosphamide plus TNF-alpha therapy: phenotypic and functional characterization up to 20 months after initial tumor inoculation.
Int J Cancer. 1998 May 18;76(4):579-86. Unique Identifier : AIDSLINE MED/98250019 Ehrke MJ; Verstovsek S; Pocchiari SK; Krawczyk CM; Ujhazy P; Zaleskis G; Maccubbin DL; Meer JM; Mihich E; Department of Experimental Therapeutics, Grace Cancer Drug Center,; Roswell Park Cancer Institute, Buffalo, NY 14263, USA.; Ehrke@SC3101.Med.Buffalo.edu
Abstract:
As reported previously, cyclophosphamide plus tumor necrosis factor-alpha treatment of C57BL/6 mice bearing advanced EL4 lymphoma induced approx. 60% long-term (i.e., >60 days) survivors. These mice developed protective immunity, as evidenced by 1) rejection (100% survival) of EL4 tumor re-implanted on day 60 (day 0 = initial tumor implantation); and 2) development of significant levels of specific EL4 tumor cell killing activity by both splenocytes and thymocytes. Using this model, age-related changes in functionally and phenotypically definable thymocyte subsets were assessed. In thymocytes from 90 to 308 day survivors, specific immune memory was long term; both CD4+ and CD8+ cells were required for the ex vivo stimulation of lytic activity, but the specific anti-EL4 cytotoxic effector was CD4-CD8+. On day 520, the surviving mice were randomized into 2 groups. One group received a second re-challenge with EL4 tumor cells and all survived. The other group was sacrificed on day 520. Their thymocytes, exposed to X-irradiated EL4, developed anti-EL4 lytic activity and, in comparison with thymocytes of young and age-matched control mice, were markedly enriched in CD4-CD8+CD44+ cells. On day 625, thymocytes from the survivors of the day 520 re-challenge were evaluated and were found to have developed specific anti-EL4 lytic activity. Phenotypically, they had returned toward the pattern seen in age-matched control mice although CD4-CD8+CD44+ cells remained increased. These mice were > or = 2 years old, the median life span of C57BL/6 mice. Thus, mice cured of tumor by an immuno-modulating regimen rejected re-implanted primary tumor and maintained specific thymic anti-tumor immune memory for life.
Keywords: *Antineoplastic Agents, Combined/THERAPEUTIC USE *Cyclophosphamide/THERAPEUTIC USE *Leukemia, Myeloid/IMMUNOLOGY *Tumor Necrosis Factor/THERAPEUTIC USE 980830
M9881117
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Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.
