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Autologous HER2 CMV bispecific CAR T cells are safe and demonstrate clinical benefit for glioblastoma in a Phase I trial.
  1. Nabil Ahmed1,
  2. Vita Brawley2,
  3. Meenakshi Hegde2,
  4. Kevin Bielamowicz2,
  5. Amanda Wakefield1,
  6. Alexia Ghazi1,
  7. Aidin Ashoori1,
  8. Oumar Diouf1,
  9. Claudia Gerken1,
  10. Daniel Landi1,
  11. Mamta Kalra1,
  12. Zhongzhen Yi3,
  13. Cliona Rooney1,
  14. Gianpietro Dotti1,
  15. Adrian Gee1,
  16. Helen Heslop2,
  17. Stephen Gottschalk1,
  18. Suzanne Powell4,
  19. Robert Grossman4,
  20. Winfried Wels5,
  21. Yzonne Kew4,
  22. David Baskin4,
  23. Jonathan Zhang4,
  24. Pamela New4 and
  25. John Hicks4
  1. Aff1 grid.39382.33000000012160926XDepartment of PediatricsCenter for Cell and Gene Therapy, Baylor College of Medicine Houston TX USA
  2. Aff2 grid.39382.33000000012160926XBaylor College of Medicine Houston TX USA
  3. Aff3 grid.39382.33000000012160926XBaylor College of Medicine/Texas Children's Hospital Houston TX USA
  4. Aff4 grid.63368.380000000404450041Houston Methodist Hospital Houston TX USA
  5. Aff5 CGT Frankfurt Frankfurt Germany

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Meeting abstracts

Glioblastoma (GBM) remains incurable with current standard-of-care therapies. Adoptive T cell transfer holds the promise to improve outcomes for GBM patients. We report on the results of the Phase I clinical study, NCT01109095, administering autologous CMV.pp65 T cells grafted with a second generation HER2 chimeric antigen receptor (CAR) with a CD28.zeta signaling domain to patients with progressive GBM.

Seventeen CMV-seropositive patients with radiologically progressive HER2+ GBM were enrolled. The median age was 49 years (range 11 to 71; 6 children; 11 adults). Children enrolled had significantly larger tumor volumes at infusion. A cell product was successfully generated for all patients from a peripheral blood draw (maximum 90mL). A median of 67% (range: 46-82) of T cells expressed the HER2 CAR, and exhibited a median 985.5 (range 390 to 1292) CMV.pp65 reactivity in an IFN-γ Elispot assay (SFC/105 T cells). Infusions of 1x106/m2-1x108/m2 were well tolerated without severe adverse events or cytokine release syndrome. HER2 CMV T cells were detected in the peripheral blood for up to 12 weeks post infusion, as judged by rtPCR of a CAR-specific amplicon. Out of 16 evaluable patients, 8 had progressive disease, 8/16 patients had objective responses: 1 patient had a partial response with a ~62% reduction in tumor volume lasting 8 months, 7 patients had stable disease for more than 6 weeks (of these 5 were durable >10 weeks) and 3 subjects are currently with a follow up 24 to >30 months, after T cell infusion. The median survival was 11.6 months from infusion and 24.8 months from diagnosis. The median survival for adults was 30 months from diagnosis.

We conclude that systemically administered HER2 CAR CMV bispecific T cells are safe. A durable clinical benefit was observed in ~38% of patients.

Trial Registration Identifier NCT01109095