TY - JOUR
AU1 - Monterroza, Lenore
AU2 - Munoz, Luis
AU3 - Bommireddy, Ramireddy
AU4 - samaranayake, Sarah
AU5 - Pack, Christopher
AU6 - Selvaraj, Periasamy
AU7 -
AB - Abstract
Metastatic triple-negative breast cancer (TNBC) has a poor prognosis primarily due to metastatic potential and resistance to currently available therapies. Recent studies suggest that TNBC may be a viable target for immunotherapy due to the presence of high levels of infiltrating lymphocytes. However, many TNBC patients do not respond due to high intra-tumoral and inter-patient heterogeneity. Utilizing a novel protein transfer method, we generate a personalized vaccine based on tumor membrane vesicles (TMVs) derived from whole tumor tissues modified with glycolipid-anchored forms of the immunostimulatory molecules (GPI-ISMs) B7-1 and IL-12. In prior studies we observed that simultaneous delivery of TMVs along with biological adjuvants enhanced CD8 T cell immunity. Herein, we investigated the impact of standard-of-care (SOC) chemotherapy on the resulting quality of the TMV vaccine. Mice were injected with 4T1 TNBC cells subcutaneously and treated with three rounds of SOC drugs starting at day 15. Chemotherapies affected tumor growth to varying degrees. Mice were euthanized and tumors were harvested for TMV preparation. Results show that depending on the treatment, the yield and particle size of TMVs was impacted. While SOC drugs affected some surface markers on TMVs, expression of CD24 and CD11b was unchanged. Further, there was reduced uptake of TMVs by dendritic cells prepared from cisplatin and 5-fluorouracil treated tumors. GPI-ISMs were equally incorporated by protein transfer onto TMVs despite SOC treatments. In summary, our studies in the 4T1 model show that a TMV vaccine can be successfully prepared after chemotherapy, but the impact on TMV yield and size justifies further investigation.
Supported by R01 CA202763
TI - Effect of Standard of Care Treatment on Tumor Membrane Vesicle Vaccine for Triple-Negative Breast Cancer
JF - The Journal of Immunology
DO - 10.4049/jimmunol.208.supp.66.19
DA - 2022-05-01
UR - https://www.deepdyve.com/lp/crossref/effect-of-standard-of-care-treatment-on-tumor-membrane-vesicle-vaccine-HuWu1RNW1z
SP - 66.19
EP - 66.19
VL - 208
IS - 1_Supplement
DP - DeepDyve
ER -