In Vivo Models of PD-1/PD-L1 axis blockade

While targeting the PD1/PDL1 axis with therapeutic antibodies (eg. nivolumab / atezolizumab) offers unprecedented clinical benefit in metastatic melanoma and lung cancer, durable responses are observed only in a fraction of patients. Current lines of investigations on such therapies mainly aim at evaluating and identifying novel drugs capable of leveraging the efficacy of PD-1/PD-L1 axis blockade. In this respect, Explicyte offers a range of syngeneic mice models of anti-PD-1 and/or anti-PD-L1 antibody therapy. Furthermore, preclinical efficacy data can be strengthened by ancillary immune cell profiling and MOA studies – relying on key immunological markers quantification, within the tumor or in peripheral organs - thereby allowing a deep interrogation of the immune response elicited by test compounds. Our models can also support for the identification of innovative and novel predictive biomarkers.

Robust preclinical models of anti-PD-1 /anti-PD-L1 antibody therapy

  • Robust treatment protocols using classical well-described antibody clones, in line with published literature data
  • Syngeneic tumor models - to evaluate drug effects on the anti-tumor immune response in the presence of a functionally immunocompetent system.
  • Anti-PD-L1 responding & non-responding tumor models, including colon, melanoma, and unique bioluminescent glioblastoma cancer models. 

Illustrative data

Differential PD1/PDL1 blockade efficacy in different syngeneic mouse models
PD1/PDL1 blockade enhances survival of MC38, moderately that of GL261, but very slightly that of CT26.

Mice are challenged with respective tumor cells and exposed to anti-PD1 or anti-PDL1 antibody. In the MC38 responding model, both anti-PD1 and anti-PDL1 antibodies improve mouse survival. 

PD1/PDL1 blockade enhances survival of MC38, moderately that of GL261, but very slightly that ...

Tumor infiltrating lymphocytes profiling of MCA205 tumor-bearing mice upon anti-PDL1 blockade
Flow cytometry analysis of MCA205 tumors highlights a higher immune cell infiltration within the tumor upon PDL1 blockade.

Anti-PDL1 antibody treatment of MCA205-timor bearing mice leads to a higher number of Tumor infiltrating lymphocytes (CD45+). This feature is associated with an increase in T cells (CD3+) and particularly with an accumulation of effector T cells (CD8+). In contrast, CD4+ T cells infiltration of the tumor is slightly decreased upon treatment.

Flow cytometry analysis of MCA205 tumors highlights a higher immune cell infiltration within ...

In vivo efficacy and profiling of anti-tumor immune response

  • Standard package: Tumor growth, body weight and survival are monitored 3 times per week in experimental groups of standardly 10 mice, including groups exposed to test compound alone and in combination with anti-PD-1 or anti-PD-L1 therapy.
  • Immune profiling package: Satellite mice (N=4) can be added to each group to evaluate the immune cell response and study how cancer therapies perform in terms of tumor-host immune interactions, at the tumor site and in peripheral compartments.
  • Quantitative multiplex immunological analysis: validated immune markers (eg. CD4, CD8, FoxP3, CD11b, CD11c, Gr1, PD-1, PD-L1…) can be analyzed appropriately using either flow cytometry, RT-qPCR, and/or immunohistology-based imaging, to delineate the in vivo mechanism(s) of action of drug candidates.

Our added-value

  • Fast study initiation and weekly progress reports: Tumor models are quickly set up upon agreement and the first progress report is sent within 10 days of the study initiation. Weekly reports enable to get the progressive achieved data, in conjunction with the Sponsor, and to adjust if necessary the study design, depending on the results.
  • Longitudinal mice bleeding: blood samples can be collected every week, allowing the evaluation of peripheral markers overtime or at given analysis time-points in responding and non-responding animals.
  • A unique expertise in syngeneic tumor models of immune checkpoint inhibition: in addition to anti-PD-1 and anti-PD-L1 immunotherapy models, we offer a range of in vivo tumor models of CTLA-4 blockade & Immunization.