Sunitinib, a
protein tyrosine kinase inhibitor is the frontline
therapy for renal and
gastrointestinal cancers. We hypothesized that by virtue of its well documented
tumor apoptosis and immune adjuvant properties, combination of
Sunitinib with anti-
tumor immunotherapeutics will provide synergistic inhibition of
tumor growth. Our study was designed to evaluate the impact of
Sunitinib on
immunotherapy mediated anti-
tumor immune responses and evaluate its efficacy as a combinatorial
therapy with
tumor targeted immunotherapeutic vaccination. Mice immunized with recombinant α-
lactalbumin, a lactation
protein expressed on majority of
breast tumors were treated with 1 mg of
Sunitinib for seven consecutive days beginning (1) concurrently, on the day of α-
lactalbumin immunization or (2) sequentially, on day 9 after immunization. Ten-day lymph nodes or 21 day spleens were tested by ELISPOT assays and flow cytometry to evaluate responsiveness to α-
lactalbumin immunization in presence of
Sunitinib and distribution of cells involved in T cell
antigen priming and proliferation in different lymphoid compartments. In addition, therapeutic efficacy of the α-
lactalbumin/
Sunitinib combination was evaluated by monitoring
tumor growth in the 4T1 transplanted
tumor model. Our studies reveal that concurrent administration of
Sunitinib with active vaccination against a targeted
tumor antigen inhibits priming to the immunogen due to a drastic decrease in CD11b+
CD11c+ antigen presenting cells, leading to failure of vaccination. However, sequential delivery of
Sunitinib timed to avoid the priming phase of vaccination results in the desired vaccination mediated boost in immune responses.