Preliminary evidence that the allogeneic response might trigger antitumour immunity in patients with advanced prostate cancer

• Published in: BJU international Vol. 98; no. 5; pp. 989 - 995
• Main Authors: Muir, Gordon, Rajbabu, Krishnamoorthy, Callen, Charles, Fabre, John W.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.11.2006; Blackwell
• Subjects: Aged; Aged, 80 and over; allogeneic response; Biological and medical sciences; genetic instability; Gynecology. Andrology. Obstetrics; Humans; Immunotherapy - methods; Lymphocyte Activation - immunology; Male; Male genital diseases; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; prostate cancer; Prostate-Specific Antigen - blood; Prostate-Specific Antigen - immunology; Prostatic Neoplasms - immunology; Prostatic Neoplasms - therapy; skin allografts; Skin Transplantation - immunology; T-Lymphocytes - immunology; Transplantation, Autologous; Treatment Outcome; Tumors; Tumors of the urinary system; tumour immunotherapy; tumour neo‐antigen; Urinary tract. Prostate gland; Antineoplastic agent; Human; tumour immunotherapy; Nephrology; Urinary system disease; Immune response; allogeneic response; Prostate disease; Homograft; skin allografts; Malignant tumor; Genetic instability; Urology; Isoimmunization; tumour neo-antigen; Treatment; Surgery; Immunotherapy; Graft; Genetics; Advanced stage; Skin; Male genital diseases; Prostate cancer
• ISSN: 1464-4096; 1464-410X
• DOI: 10.1111/j.1464-410X.2006.06421.x

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. PATIENTS AND 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. CONCLUSION 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.