Date of Award
Open Access Thesis
Medical Doctor (MD)
In the photopheresis therapy for cutaneous T-cell lymphoma, malignant T-cells exposed to 8-methoxypsoralen (8-MOP) activated by ultraviolet A (UVA) light appear to induce an immunologic response against the malignancy. In order to investigate this response, we used T-cell hybridoma 2B4.11 in genetically compatible (AKR X B10 .A) F1 hybrid mice as a murine model for T-cell lymphoma. We compared the ability of cells inactivated by 8-MOP/UVA, mitomycin C (MMC)3 glutaraldehyde, and X-irradiation to immunize against tumor.
[3H]-thymidine-uptake assays determined the doses of 8-MOP/UVA, MMC, glutaraldehyde, and X-irradiation necessary for inactivation of 2B4.11 cells. Mice then were subjected to an immunization protocol consisting of four weekly intraperitoneal injections of 5x10 6 inactivated 2B4.11 cells followed by challenge with 5x10 6 viable 2B4.11 cells. Of mice challenged 6 days after the end of the immunization protocol, only the recipients of cells inactivated by 8-MOP/UVA and MMC showed a significant enhancement of 80-day survival (50% alive in 8-MOP/UVA group, 40% in MMC group, 0% in control group; p<0.05). Mice treated with 8-MOP/UVA-inactivated cells were challenged 30 days after the end of the protocol; enhancement of 80-day survival was very significant (87.5% alive vs. 0% in controls; p<0.01). Mice identically treated were challenged either with 2B4.11 or with related hybridoma C10.9; there was no significant cross-protection. C3H nu/nu athymic mice were subjected to the same immunization protocol; only recipients of cells damaged by X-irradiation demonstrated significant enhancement of 80-day survival (75% vs. 0% in controls). No cytotoxic cells were evident among splenocytes taken directly from immune mice or after in vitro stimulation with irradiated 2B4.11 in 51 Cr-release assays.
We conclude that 8-MOP/UVA-inactivated 2B4.11 cells induce an immune response that is more active at thirty days after immunization than at six days; is not significantly cross-protective against hybridoma C10.9; and appears to be at least partially mediated by non-T-cell elements.
Lobo, Francis M., "T-cell Tumor Prevention by Treatments with Psoralen/UVA-Inactivated Tumor Cells" (1992). Yale Medicine Thesis Digital Library. 3556.
This Article is Open Access