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.
Dzojic
Helena
H
Clinical Immunology Division, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
Loskog
Angelica
A
Tötterman
Thomas H
TH
Essand
Magnus
M
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