Rajiv Khanna (QIMR Berghofer Medical Research Institute, Australia)
“Adoptive T Cell Therapy for NPC: Immune Correlates to Immune Contexture”
- Collaborates with Victor Lee, Dora Kwong, Hohn Nichols, Vivian Li, Daniel Chua, Randall ‘Tis Janice Tsang … at HKU)
- 2017/10/20 second CD19 CAR-T
- NPC T cell immunotherapy in the past 10 years
- Singapore group
- Adoptive T cell transfer and chemotherapy in the first line treatment of metastatic NPC
- EBV T cell immunotherapy (emerging developments)
- ASTRA BIO; Tab-celTM; PTLD
- TESSA Therapeutics; EBV ST; NPC
- Manufacturing process for autologous T cell therapies for NPC
- Step 1 synthetic peptide or viral vector (expressing viral antigen) or EBV-LCL + peripheral blood mononuclear cells+ IL2
- Step2 T cells +IL2 antigen specific T cells
- Step 3 Micro Multiepitope technoology: E1-LMPpoly
- Adenochimera chimera
- Polyepitope of LMP1 and 2 HLA class I CD8+ T cells peptide epitope conjugated to a truncated EBNA1 gene and incorporated into adenoviral vector
- In vitro expansion of EBV-specific T cells from EBV+nasopharyngeal carcinoma patients
- Other antigens (LMP1, LMP2).
- ARMD NPC (stage IUV NPC patients (multiple Kline’s of therapy, ; N/MRD: no or minima residual disease)
- T cell characteristics and response to T n cell therapy
- Post EBV-specific T cell therapy and progression disease fress and overall survival
- Immunotherapy: to resond or not to respond, that is the question
- why some cancers show better clinical response to immunotherapy while other malignancies remain un-responsive
- Clinical response to immunotherapy
- 1. Cancer (TME)
- 2. Immunotherapy-drug produce (potency/delivery)
- 3. Patient (immunological status)
- immune contexture of cancer er and repind to immunotherapy
- multiplex IHC using tyrmide signal amplification
- Immuno contexture analysis using multiplexed panels
- Panel 1 CD8, PDL1, TIM-3, T-bel,
- Multiplexed immunohistochemistry (Reshma Shakya)
- Intra-tumoral PD-L1 expression and clinical response to checkpoint
- Future immunological intervention for NPC patients based on PD-L1 expression
- PD-1 high -> anti-PD1
- Next a generation “off-the-shelf” EBV T cell therapy manufacturing and distribution
- Proprietary algorithm (1-2 alleles are enough)
- 17 studies (281 patients treated 64% CR +10.7% PR)
- AdE1-LMPpily “off-the-shelf” T cell therapy for NPPC and gastric cancer
- Ratio of CD8+ top CD4+FoxoP Tim3+
- Uniquely PD-1 low –> ACT
- Qualitative profile of EBV-specific T cells impacts on the clinical response of NPC patients