(787) Intratumoral administration of Sequential Heterologous Vaccine followed by intratumoral IL-15 complexes induces complete anti-tumor responses.

Introduction/Rationale: In the context of TNBC, the premise of exploiting heterologous vaccine dosing is particularly intriguing. The immune system, when effectively activated and directed, can serve as a potent arbiter of anti-tumor activity. Sequential administration of heterologous vaccines could harness the immune system's inherent plasticity to generate a comprehensive anti-tumor response. Leveraging the immunogenicity and unique compositions of vaccines traditionally employed against infectious agents, such as Shingrix (Zoster Vaccine Recombinant, Adjuvanted), and HEPLISAV-B (a CPG adjuvanted hepatitis B vaccine), may provide a unique opportunity to modulate the tumor microenvironment in TNBC.

Methods: BALB/c mice with induced 4T1 tumors were treated intratumorally with a sequence of HEP B, SHINGRIX, and SHINGRIX (HSS) vaccines given on consecutive days intratumorally.

Results: Tumor growth kinetics revealed that the HSS Sequence significantly inhibited tumor growth, with 4 out of 5 mice remaining tumor-free 60 days post-tumor induction. Moreover, when the HSS sequence vaccine was combined with intratumoral administration of IL-15 complexes, our results show that complete tumor regression and long-term immunity were established. While tumor growth was significantly delayed when anti-PD-1 was added intraperitoneally alone to the HSS sequence vaccine, only two out of five mice remained tumor-free 60 days post-tumor induction. When the HSS sequence vaccine, IL-15, and anti-PD1 were combined, tumor growth was significantly reduced, with 4 of 5 mice remaining tumor-free 60 days post-tumor induction.

Conclusion: These data suggest an optimized immunotherapeutic strategy combining vaccine sequencing with IL-15 complexes in TNBC. These data demonstrate the promise of in situ pathogen vaccine combination, either alone or in combination with IL-15 complexes, as a potent anti-cancer approach, eliminating the need for anti-PD1 therapy.