4.6 Article

Synergistic antitumor response with recombinant modified virus Ankara armed with CD40L and CD137L against peritoneal carcinomatosis

Journal

ONCOIMMUNOLOGY
Volume 11, Issue 1, Pages -

Publisher

TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2022.2098657

Keywords

Peritoneal carcinomatosis; CD40L; CD137L; CD8 immune response; cancer immunotherapy

Funding

  1. Instituto de Salud Carlos III [PI20/00002, PI19/01128]
  2. Fondos FEDER A way to make Europe [TRANSCAN456, TRS-2016-00000371]
  3. Gobierno de Navarra [0011-1411-2020-000075]
  4. European Union [765394, CP19/00114]
  5. ISCIII (Instituto de Salud Carlos III) - FSE (Fondo Social Europeo)
  6. PFIS fellowship from ISCIII [FI20/00058]
  7. Aid Program Assigned to Projects from the University of Navarra
  8. Spanish Association Against Cancer's (AECC) Investigator grant [INVES19041ALVA]
  9. Marie Curie Actions (MSCA) [765394] Funding Source: Marie Curie Actions (MSCA)

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This study evaluated different recombinant-modified vaccinia virus Ankara (rMVA) vectors in preclinical peritoneal carcinomatosis models and found that the vector encoding both CD40L and CD137L can enhance immune response and improve survival in mice with peritoneal carcinomatosis.
Recombinant-modified vaccinia virus Ankara (rMVA) is known to elicit potent antitumor immune responses in preclinical models due to its inherent ability to activate the innate immune system and the activation of adaptive responses mediated by the expression of tumor antigens and costimulus-providing molecules, such as CD40L and CD137L. Here, we evaluated different rMVA vectors in preclinical peritoneal carcinomatosis models (ID8.OVA-Vegf/GFP and MC38). We compared rMVA vectors expressing a tumor antigen (OVA or gp70) either alone or co-expressed with CD40L or/and CD137L. In tumor-free mice, the vector coding for the triple combination was only slightly superior, whereas, in tumor-bearing animals, we observed a synergistic induction of T lymphocytes specific against vector-encoded and non-encoded tumor-associated antigens. The enhanced activation of the immune response was associated with improved survival in mice with peritoneal carcinomatosis treated with a rMVA vector encoding both CD40L and CD137L. Thus, the triple transgene combination in vaccinia viral vectors represents a promising strategy for the treatment of peritoneal carcinomatosis.

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