Slide 1: Targeting Lymphomas Using Non-Engineered, Multi-Antigen Specific T Cells
Targeting Lymphomas Using Non - Engineered, Multi - Antigen Specific T Cells George Carrum, Premal Lulla, Ifigeneia Tzannou, Ayumi Watanabe, Manik Kuvalekar, Munu Bilgi, Tao Wang, Rammurti Kamble, Carlos A. Ramos, Rayne Rouce, Bambi J. Grilley, Adrian P. Gee, Malcolm K. Brenner, Helen E. Heslop, Cli
Slide 2: Adoptive T cell transfer overview
Infusion Tumor - specific T cells Antigen Specificity Patient Adoptive T cell transfer Blood draw PBMCs
Slide 3: Our approach
• Simultaneously target multiple TAAs • Target multiple epitopes (CD4 and CD8) within each antigen • T cells with native T cell receptor specificity (non - engineered) Our approach
Slide 4: MultiTAA T cell therapy for lymphoma
MultiTAA T cells MultiTAA T cell therapy for lymphoma MAGEA4 PRAME Survivin NYESO1 SSX2
Slide 5: MultiTAA-T Cell manufacture
Activation DC Overlapping pepmixes PBMCs MultiTAA T cells Expansion MultiTAA - T Cell manufacture
Slide 6: MultiTAA-T Cell Phenotype
0 20 40 60 80 100 % Positive cells MultiTAA - T Cell Phenotype n=39 CD4 CD8 CD3 DC TCM TEM NK
Slide 7: MultiTAA-T Cell Specificity
SFC/2x10 5 cells MultiTAA - T Cell Specificity SSX2 MAGEA4 PRAME Survivin NYESO1
Slide 8: MultiTAA-T Cell Autoreactivity
% Specific Lysis Multi TAA - T Cell Autoreactivity E:T of 20:1
Slide 9: Clinical Trial: Eligibility
Any patient > 18 yrs with HL or NHL Active disease - in 2 nd or subsequent relapse - in 1 st relapse for indolent lymphoma after 1 st line therapy for relapse - in 1 st relapse if immunosuppressive chemotherapy contraindicated - primary refractory disease or persistent disease after 1 st line therap
Slide 10: Safety of MultiTAA T cells - Antigen escalation
Antigen Escalation Phase = fixed dose 5x10 6 /m 2 – 2 pts/stage : Day 0: PRAME - specific T cells Day 28: PRAME and SSX - specific T cells Stage Two : Day 0: PRAME and SSX - specific T cells Day 28: PRAME/SSX/MAGE - specific T cells Stage Three : Day 0: PRAME/SSX/MAGE - specific T cells Day 28: PRAM
Slide 11: Safety of MultiTAA T cells - Dose escalation
PRAME/SSX/MAGE/NYESO1/Survivin - specific T cells : 2 - 4 pts at each level, 2 infusions 14 days apart Dose Level 1 : Day 0 and 14: 5x10 6 cells/m 2 Dose Level 2 : Day 0 and 14: 1x10 7 cells/m 2 Dose Level 3 : Day 0 and 14: 2x10 7 cells/m 2 Safety of MultiTAA T cells - Dose escalation
Slide 12: Clinical Trial: Treatment
Clinical Trial: Treatment • 33 patients infused
Slide 13: Clinical Trial: Treatment
Antigen escalation (n=4) Antigen escalation (n=4) Dose escalation (n=14) Dose escalation (n=11) Clinical Trial: Treatment Group B: Active lymphoma (failed prior lines) Group A: In remission • 33 patients infused
Slide 14: Clinical Trial: Treatment
- 33 patients infused (0.5 - 2x10 7 cells/m 2 ) - 12 HL - 19 aggressive NHL (DLBCL/mantle/peripheral T) - 2 with composite lymphoma - No lymphodepletion - No adverse events Clinical Trial: Treatment
Slide 15: Pt1 (HL) – Clinical and Immune effects
0 20 40 60 80 100 120 140 Pre Post Non - targeted antigens NYESO1 AFP Non - targeted antigens Pt1 (HL) – Clinical and Immune effects Post CTLs + radiation 0 10 20 30 40 50 60 70 80 90 Prame SSX2 MAGE A4 NYESO - 1 Survivin No pep Pre #1 wk1 wk2 Pre #2 mth3 S F C / 5 x 1 0 e 5 A B Pre T cells Post CTL
Slide 16: Pt2 (NHL) – Clinical and Immune effects
0 20 40 60 80 100 120 140 160 180 200 PRE MTH3 MTH9 Survivin NYESO1 MAGEA4 SSX2 PRAME SFC/2x10 5 Pre Mth3 Mth9 Targeted antigens Non - targeted antigen Mth 3 Mth 9 Pre - Infusion 0 5 10 15 20 25 30 35 40 45 Pre Mth3 Mth9 MAGEC1 SFC/2x10 5 Pt2 (NHL) - Clinical and Immune effects
Slide 17: Clinical Outcomes – Adjuvant
- 18 patients infused as adjuvant - 15/18 in remission (median 19 months) Clinical Outcomes – Adjuvant Clinical Outcomes – Adjuvant
Slide 18: Clinical Outcomes – Adjuvant
Clinical Outcomes – Adjuvant ID Age/Sex Disease Prior Therapies Response to T cell therapy (duration) 1 * 39/M HL & DLBCL ABVD RICE ASCT CCR (>3 years) 2 * 78/F DLBCL R RCHOP In remission (8 mo ) relapse 3 * 78/F DLBCL R RCHOP multiTAA T cells R - Bendamustine CCR (>3 years) 4 * 21/M H
Slide 19: Clinical Outcomes – Active disease
- 15 patients treated for active disease - 6 CRs; 4 SD; 5 PD Clinical Outcomes – Active disease
Slide 20: Clinical Outcomes – Active disease
Clinical Outcomes – Active disease ID Age/Sex Disease Prior Therapies Response to multiTAA T cells (duration) 1 * 31/F HL ABVD ICE Cis - Gem XRT ASCT EBV T cells Brentuximab Yttrium90 CART - CD30 Stable disease (5 mo) Off study [ Revilimid (5 mo ) PD1] 2 * 55/F HL/NHL RCHOP + XRT
Slide 21: Summary to date
• Safe to date • Feasible adjuvant and treatment • In vivo expansion of T cells directed to targeted antigens • Antigen/Epitope spreading • Clinical benefit Summary to date
Slide 22: Targeting Lymphomas Using Non-Engineered, Multi-Antigen Specific T Cells
Targeting Lymphomas Using Non - Engineered, Multi - Antigen Specific T Cells George Carrum, Premal Lulla, Ifigeneia Tzannou, Ayumi Watanabe, Manik Kuvalekar, Munu Bilgi, Tao Wang, Rammurti Kamble, Carlos A. Ramos, Rayne Rouce, Bambi J. Grilley, Adrian P. Gee, Malcolm K. Brenner, Helen E. Heslop, Cli