Adoptive Immunotherapy Combined with Hematopoietic Cell Transplantation as a Therapeutic Treatment of Prostate Cancer

摘要

We determined that a prostate cell lysate prepared from canine prostate tissue was immunogenic when injected in female dogs. In addition to the known prostate antigen, canine prostate specific esterase (CPSE), we identified by molecular weight several other proteins against which the dog made IgG antibodies. Using a mixed lymphocyte reaction, we found that a cellular response was generated against the prostate cell lysate after the female dog was injected 3 times with antigen. Sensitization of female dogs with prostate antigen suspended in incomplete Freund's adjuvant appeared to be superior to prostate lysate antigen loaded canine autologous dendritic cells when both were injected subcutaneously near the popliteal lymph node. Peripheral blood lymphocytes and lymph node derived lymphocytes reacted to prostate lysate in the mixed lymphocyte reaction. An immune response to prostate lysate not significantly detected by a delayed-type hypersensitivity reaction 24 to 48 hours after the last of three subcutaneous injections of antigen. One of four male dogs transplanted with dog leukocyte identical female bone marrow engrafted was stably engrafted. Injection of prostate antigen- sensitized female peripheral blood mononuclear cells failed to induce prostatitis, conversion of mixed to 100% hematopoietic chimerism or initiate graft versus host disease in the male recipient. Based on a single example, these results suggest that induction of an inflammatory response against normal tissue following injection of antigen sensitized lymphocytes may require additional perturbation to the recipient's targeted tissue.