AlloDC cancer immunotherapy utilizes the allogeneic reaction as an immunostimulatory adjuvant. Intratumoral alloDC vaccination reverses the immune suppressed tumor micro-environment and activates anti-tumor immune responses. Herein, we aim to examine the use of Ad5f35PTD, an infection-enhanced serotype 5 adenovirus containing fibers from serotype 35 and cell-penetrating peptides on the hexons, as a vector to deliver tumor-associated antigens to monocyte-derived immature DCs in combination with an established DC maturation cocktail. Ad5f35PTD-transduced, cocktail-matured DCs expressed co-stimulatory and activation molecules and secreted the Th-1 type cytokine IL-12, in vitro. Natural killer (NK) cells migrated better towards medium from Ad5f35PTD-transduced, cocktail-matured DCs than medium from only cocktail-matured DCs, which was in accordance with a higher CXCL-10 chemokine level. The alloDC effect was examined in vivo using mature murine DCs of BALB/c origin (D2SC/I), transduced with Ad5f35PTD encoding the melanoma-associated antigen gp100, injected subcutaneously into C57BL/6 mice. They induced a higher migration of host DCs in the draining lymph node, in comparison to the D2SC/I cells alone. The migrated host DCs efficiently presented the captured gp100 and activated gp100-specific CD8+ T-cells. Moreover, alloDCs transduced with the gp100-encoding Ad5f35PTD reduced the immunosuppressive environment when injected intratumoraly by reducing the ratio of monocytic to granulocytic myeloid-derived suppressor cell compartment and delay tumor growth in a B16 melanoma model, in comparison with the D2SC/I cells alone. Concluding, the Ad5f35PTD transduced alloDCs expressing gp100 showed potency in eliciting tumor-specific immune responses in comparison to the alloDCs alone.
Citation Format: Grammatiki Fotaki, Chuan Jin, Alex Karlsson-Parra, Di Yu, Magnus Essand. Allogeneic dendritic cells (AlloDCs) transduced with an infection-enhanced adenovirus as adjuvant for cancer immunotherapy. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr A172.
- ©2016 American Association for Cancer Research.