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Poster Display session 3

1679 - HPV16 E6-specific TCR-T armored with checkpoint blockade in the treatment of cervical cancer

Date

30 Sep 2019

Session

Poster Display session 3

Topics

Immunotherapy

Tumour Site

Presenters

Paul Bryson

Citation

Annals of Oncology (2019) 30 (suppl_5): v475-v532. 10.1093/annonc/mdz253

Authors

P. Bryson1, Q. Jia2, G. Chen3, S. li1, J. Fang1, L. Zhao4, B. Wolff4, R. Chen4, Y. Wan3, Q. Li5, B. Zhu2

Author affiliations

  • 1 Research And Development, TCRCure Biopharma Corp., 90032 - Los Angeles/US
  • 2 Institute Of Cancer, Xinqiao Hospital, Third Militrary Medical University, 400038 - Chongqing/CN
  • 3 Biomedical Analysis Center, College of Basic Medicine, Third Military Medical University (Army Medical University), 400084 - Chongqing/CN
  • 4 Research And Development, TCRCure Biopharma Corp., 27701 - Durham/US
  • 5 Department Of Immunology, Duke University, 27710 - Durham/US

Resources

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Abstract 1679

Background

Human papillomavirus 16 (HPV16) elicits cervical cancers and provides an ideal target for T cell-based immunotherapy. Although engineered T cell therapies delivered unprecedented successes in hematological cancers, treating solid cancers has been suboptimal. One key mechanism of tumor-elicited suppression is the PDL1-PD1 checkpoint which blocks T cell activation. Therefore, TCR-T cells armored with checkpoint blockades may further enhance the efficacy of TCR-T in solid cancers.

Methods

HPV16+HLA-A2+ Stage IV cervical cancer patients were consented and enrolled to a two-arm study: Arm 1 is a mono-treatment with HPV16 TCR-T, and, Arm 2 is a treatment with anti-PD1 scFv expressing HPV16 TCR-T cells. PBMCs were collected from patient by lymphocyte apheresis and a TCR targeting HLA-A2-presented E6 epitope was retrovirally transduced. This study is designed for dose escalation at three levels: 5 × 106/kg, 1 × 107/kg, and 5 × 107/kg. Initial safety and efficacy were monitored at day 7, 14, 28 post treatment, followed by long-term monthly monitoring for up to two years.

Results

By the date of submission, five patients have been treated in Arm 1: two were infused with 5 × 106/kg dose, and three were infused with 1 × 107/kg dose. Adverse effects include leukocytopenia (100%), anemia (100%), fatigue (60%), fever (40%) and thrombocytopenia (40%). One patient (20%) had Grade 4 leukocytopenia. No CRS was observed. For all five patients, TCR-T cells were engrafted, and expanded with peak responses during day 7 to 14 post-infusion. At 28 days post-infusion, three patients (60%) were assessed as SD, one patient (20%) was assessed as PD, and one patient was absent for follow-up. Two patients have been recruited for arm 2. One patient received 5 × 106/kg and one received 1 × 107/kg of anti-PD1 armored TCR-T cells. The low dose patient was assessed as SD at both day 28 and month 2 post treatment.

Conclusions

With mild and manageable sides effects, both mono and anti-PD1-armored E6-TCR-T therapies demonstrated to be safe at up to 1 × 107/kg dosage. T cells were stimulated in patients and clinical responses can be identified. These results warrant further evaluation of the safety and efficacy at higher doses.

Clinical trial identification

NCT03578406.

Editorial acknowledgement

Legal entity responsible for the study

Xinqiao Hospital, Third Militrary Medical University and TCRCure Biopharma Corp.

Funding

TCRCure Biopharma Corp.

Disclosure

All authors have declared no conflicts of interest.

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