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.
Resources from the same session
5517 - Molecular fingerprinting in breast cancer (BC) screening using Quantum Optics (QO) technology combined with an artificial intelligence (AI) approach applying the concept of “molecular profiles at n variables (MPnV)”: a prospective pilot study.
Presenter: Jean-Marc Nabholtz
Session: Poster Display session 3
Resources:
Abstract
2152 - Inferring the correlation between incidence rates of melanoma and the average tumor-specific epitope binding ability of HLA class I molecules in different populations
Presenter: Istvan Miklos
Session: Poster Display session 3
Resources:
Abstract
4382 - Thermal Liquid Biopsy as a Valuable Tool in Lung Cancer Screening Programs
Presenter: Alberto Rodrigo
Session: Poster Display session 3
Resources:
Abstract
2465 - Towards a screening test for cancer by circulating DNA analysis
Presenter: Rita Tanos
Session: Poster Display session 3
Resources:
Abstract
3788 - Evaluation of a successful launch of the MammaPrint and BluePrint NGS kit
Presenter: Leonie Delahaye
Session: Poster Display session 3
Resources:
Abstract
3863 - Analysis of prognostic factors on overall survival in elderly women treated for early breast cancer using data mining and machine learning
Presenter: Pierre Heudel
Session: Poster Display session 3
Resources:
Abstract
1993 - Circulating tumor cell detection in epithelial ovarian cancer using dual-component antibodies targeting EpCAM and FRα
Presenter: Na Li
Session: Poster Display session 3
Resources:
Abstract
4281 - CEUS of the breast: Is it feasible in improved performance of BI-RADS evaluation of critical breast lesions?——A multi-center prospective study in China
Presenter: Jun Luo
Session: Poster Display session 3
Resources:
Abstract
2268 - Classification of abnormal findings on ring-type dedicated breast PET for detecting breast cancer
Presenter: Shinsuke Sasada
Session: Poster Display session 3
Resources:
Abstract
4035 - Prediction of benign and malignant breast masses using digital mammograms texture features
Presenter: Cui Yanhua
Session: Poster Display session 3
Resources:
Abstract