in vivo tumor model of immunization

The low immunogenicity of tumor cells is one of the key mechanisms used by the tumor to escape from the immune surveillance. Thus, new cancer immunotherapeutic strategies aim at enhancing the presentation of tumor antigens to T cells. To this end, therapeutic cancer vaccines are an attractive alternative to conventional therapies (chemotherapy, immune checkpoints inhibitors, etc). We validated at Explicyte a model of immunization relying on the co-administration of adjuvants poly(I:C) (TLR3 ligand) and agonistic anti-CD40 antibody into tumor bearing mice. This immunization approach represents an attractive model to evaluate the capacity of drug candidates to boost the anti-tumor immunity.

Preclinical Models Of TLR3 ligation and CD40 activation

 

  • Syngeneic tumor models to keep intact the host immune response against the tumor, tumor cells are inoculated into immunocompetent mice.
  • A validated treatment protocol in line with the data described in the bibliography.
  • An adapted therapeutic window to evaluate potential synergistic effects with drug candidate.

MC38 tumor model of immunization with PolyIC and anti-CD40 antibody

Immunization with Poly-IC and agonistic anti-CD40 monoclonal antibody delayed survival of MC38 (colorectal) tumor bearing mice. Mice were challenged with MC38 tumor cells, and co-exposed to PolyIC and anti-CD40. Tumor growth (and survival) was followed and shown a full tumor rejection in immunized mice.

Preclinical in vivo efficacy and anti-tumor immune response profiling

 

  • Standard package includes tumor growth, body weight and survival  monitoring 3 times per week in 4 experimental groups (N=10), including vehicle, PolyIC & anti-CD40 treatment, test compound, and combination therapy (PolyIC & anti-CD40 mAb + test compound).
  • Satellite mice can be added to each experimental group and used to evaluate the impact of treatment protocol on the immunological synapse at the tumor site & in peripheral compartments.
  • Multiplex and quantitative immunological analysis: validated immune markers (eg. CD4, CD8, FoxP3, CD11b, Gr1, …) can be monitored by FACS and/or RTqPCR for deciphering the underlying in vivo mechanism of action of the test compound.

Our added-value

 

  • Fast study initiation & weekly reports: tumor models are set up and ready for treatment in less than 1 month. Progress reports are provided on a weekly basis.
  • Analysis of immunological parameters by flow cytometry: validated markers include CD4, CD8, CD25, FOXP3, CD11b, Gr1, CD11c, mPDCA1… among others
  • Expression of immune-related genes: RTq-PCR data available for some genes including Il6, Ifng, Il17, Tnfa, Tgfb, Il10, Foxp3, Rorc, Cd274 (PD-L1), Pdcd1 (PD1), …
  • A strong expertise in syngeneic tumor models: in addition to PolyIC & anti-CD40 tumor model, Explicyte offers other in vivo tumor models , including syngeneic mouse models of  CTLA-4  and PD-1/PD-L1 blockade.

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As part of its preclinical CRO services for cancer immunotherapy, Explicyte immuno-oncology has validated in vivo models of therapeutic vaccines for cancer, based on the combined immunization with anti-CD40 antibody and Poly IC adjuvant. Syngeneic mouse tumor models are thus treated with a combination of toll-like receptor (TLR) agonist poly(IC) combined and a stimulatory anti-CD40 monoclonal antibody.