Adenovirus-mediated CD40 ligand therapy induces tumor cell apoptosis and systemic immunity in the TRAMP-C2 mouse prostate cancer model.
BACKGROUND
The interaction between CD40 ligand (CD40L) and CD40 on antigen presenting cells is essential for the initiation of antigen-specific T-cell responses, whereas CD40L stimulation of CD40+ tumor cells can induce cellular apoptosis. We investigated the anti-tumor effects induced by CD40L gene transfer into the mouse prostate adenocarcinoma cell line TRAMP-C2, both in vitro and in vivo.


METHODS
TRAMP-C2 cells were transduced with an adenoviral vector encoding CD40L (AdCD40L). The induced expression of co-stimulatory molecules and cell viability was analyzed. AdCD40L-transduced TRAMP-C2 cells were used in prophylactic vaccination studies, while therapeutic studies were performed using peritumoral injections of AdCD40L.


RESULTS
AdCD40L yielded reduced TRAMP-C2 cell viability and induced apoptosis in vitro. Vaccination with CD40L-expressing TRAMP-C2 cells induced anti-tumor immunity and peritumoral AdCD40L injections induced tumor growth suppression.


CONCLUSIONS
Our observations highlight the therapeutic potential of using AdCD40L as a monotherapy or in combination with conventional chemotherapy or novel therapies (e.g., oncolytic viruses). The use of AdCD40L offers an attractive option for future clinical trials.
Clinical Immunology Division, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
Helena
H
Dzojic
Angelica
A
Loskog
Thomas H
TH
Tötterman
Magnus
M
Essand
D000230:Adenocarcinoma / Q000201:enzymology / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D023201:CD40 Ligand / Q000235:genetics* / Q000378:metabolism; D019496:Cancer Vaccines; D020169:Caspases / Q000032:analysis; D002460:Cell Line; D002470:Cell Survival; D004195:Disease Models, Animal; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D014161:Transduction, Genetic
D019496:Cancer Vaccines; D023201:CD40 Ligand; D020169:Caspases