Therapeutic Vaccines

Cancer therapies based on the administration of primed T-cells are being explored for a variety of malignancies.  In Burkitt's lymphoma, there is no natural CTL response, but in B-cell lymphomas caused by immunosuppression, regression is observed when CTL function is restored.  This is suggestive of a potential for raising transplant recipient CTLs in vitro and readministering to target cells.  In NPC, HD, and T-cell lymphomas, very little is known about antigen processing and presentation.  As in Burkitt's lymphoma, many of the dominant antigens against which the memory T-cell response is generated (such as EBNAs 2, 3A, 3B, 3C, and LP) are not expressed.  Any CTL responses against EBNA 1, LMP1, or LMP2 (which are expressed on tumor cells) could be used for exploitation (12).

In post-transplant lymphoproliferative disease (PTLD) patients, the above method of immunotherapy was tested by Khanna et. al. In the case of bone marrow transplantation, PTLD are exclusively of donor origin whereas in solid organ transplant patients the PTLD are usually of recipient origin. The problems associated with CTL treatment of transplant patients include the potential activation of a CTL response in vitro from an  immunosuppressed individual, the risk of increasing allospecific-specific CTL that will threaten the integrity of the transplanted organ, and the efficacy of adoptively transferred CTL in the face of high levels of immunosuppression in vivo.  Yet despite these obstacles, this study was able to show a successful example of PTLD associated lymphoma regression with the adoptive transfer of CTLs.  The protocol selected for and amplified EBV-specific CTLs which did not attack transplanted cells (13).  This study supports the possibility of PTLD treatment and could also be applied to immunodeficiencies such as X-linked immunodeficiency disorder and HIV-EBV infected persons.

Cancer regression in a CTL adoptive transfer experiment:
A. liver scan before CTL therapy showing two lymphomas
B. two weeks after first CTL infusion
C. twenty weeks after first infusion and before fourth CTL infusion revealed complete regression.
-taken from Khanna et al., citation 13 below.
 

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