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120 P-MUC1C-ALLO1: An allogeneic car-t for multiple solid tumor indications
  1. Anna Kozlowska,
  2. Yan Zhang,
  3. Jacqueline Fritz,
  4. Steven Wang,
  5. Rebecca Codde,
  6. Elvira Argus,
  7. Samad Ibitokou,
  8. Vanitra Richardson,
  9. Sumiti Jain,
  10. Maximilian Richter,
  11. Deepak Patil,
  12. Yening Tan,
  13. Min Tong,
  14. Lu Yao,
  15. Majid Ghoddusi,
  16. Eric Ostertag,
  17. Julia Coronella and
  18. Devon Shedlock
  1. Poseida, San Diego, CA, USA


Background MUC1 is a highly glycosylated protein that is expressed at the apical border of mucosal epithelium where it plays a protective role. MUC1 is comprised of an N-terminal subunit (MUC1N) tethered to a C-terminal subunit (MUC1C), forming a stable complex on the cell surface. A proteolytic ‘stump’ of MUC1C that may be aberrantly glycosylated is over-represented in cancer, making it an attractive therapeutic target. Here we report generation of allogeneic MUC1C-specific CAR T cells, P-MUC1C-ALLO1, that are designed to leverage the learnings of our P-BCMA-ALLO1 program. P-MUC1C-ALLO1 targets a MUC1C epitope and has the potential for efficacy against a wide range of solid tumors, without targeting normal epithelial cells.

Methods mRNA-generated MUC1C CAR-T cells were evaluated for specificity and function by degranulation assay against various solid tumor and normal cells and cell lines. Autologous and allogeneic MUC1C CAR-T cells were produced using the piggyBac® DNA Modification System, a nonviral CAR-T manufacturing method that produces CAR-T products with an exceptionally high percentage of T stem cell memory (TSCM) cells. To produce allogeneic cells, multiplex editing of both TRBC and B2M was performed with the Cas-CLOVER™ Site-Specific Gene Editing System to reduce or eliminate GvHD and host versus graft alloreactivity, respectively. To determine in vivo antitumor efficacy of MUC1C CAR-T cells, we employed the MDA.MB.468 triple negative breast cancer model and the OVCAR3 disseminated ovarian cancer model.

Results Specific degranulation of transiently-expressing CAR+ T cells was observed against multiple tumor cells, with no observable activity against normal human primary cells. In assay of stable P-MUC1C-101 CAR-T cells, more than 95% expressed CAR, and were comprised of an exceptionally high-percentage of TSCM cells (CD45RA+CD62L+CD45RO-). In vitro, P-MUC1C-ALLO1 cells specifically proliferated, lysed, and secreted IFN-γ against MUC1C+ breast and ovarian tumor cell lines. In breast cancer in vivo xenograft model, both unedited (MUC1C CAR-T) and edited (P-MUC1C-ALLO1) MUC1C CAR-T eliminated established, triple negative MDA.MB.468 tumor cells to undetectable levels, demonstrating the efficacy of the MUC1C CAR-T and the robustness of the allogeneic platform. In the OVCAR3 xenograft model, intraperitoneally administered MUC1C CAR-T eliminated established tumor cells to levels below the limit of detection.

Conclusions P-MUC1C-ALLO1 is Poseida’s allogeneic CAR TSCM product that has a potential to treat multiple MUC1-expressing indications. P-MUC1C-ALLO1 displayed in vitro specificity for tumor vs normal cells, and in vivo efficacy against xenograft models of breast and ovarian cancer. We anticipate an IND filing and initiation of a Phase 1 clinical trial in 2021.

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See:

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