Preliminary evidence that the allogeneic response might trigger antitumour immunity in patients with advanced prostate cancer.
OBJECTIVE
To explore the possibility that allogeneic responses might, by chance, encompass cross-reactive T cell clones specific for neo-antigenic tumour determinants, and thereby activate antitumour immunity; such cross-reactions are well documented for antiviral immunity, and genetic instability in developing cancers generates many neo-antigenic determinants as potential targets for immune responses, but the biology inevitably favours tumour progression.


METHODS
Fourteen patients with hormone-refractory prostate cancer received full-thickness skin allografts from different, unrelated donors (fellow patients) until each had received six grafts. Serum prostate-specific antigen (PSA) level was used as a surrogate for tumour mass.


RESULTS
One patient had a remarkable decline in PSA level, with levels at 1 year lower than before grafting. A second patient had stable PSA levels for almost 2 years. A third patient had stable PSA levels for 10-12 months before they resumed an exponential rise. Of four patients with PSA levels of > 10 ng/mL, three required surgery or radiotherapy for obstructive symptoms during or shortly after grafting.


CONCLUSIONS
Transplant rejection involves mechanistically atypical T cell recognition of allogeneic major histocompatibility complex antigens, with massive polyclonal T cell activation. This unique aspect of T cell biology might represent a novel approach for initiating cross-reactive antitumour responses.
Muir
Gordon
G
Department of Urology, King's College Hospital, London, UK.
Rajbabu
Krishnamoorthy
K
Callen
Charles
C
Fabre
John W
JW
D000368:Aged; D000369:Aged, 80 and over; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000276:immunology / Q000628:therapy*; D016038:Skin Transplantation / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D017430:Prostate-Specific Antigen