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1 Supplemental table 1. Overview of recent clinical phase I and II trials assessing the safety and efficacy of TCR-modified T cells in cancer patients as registered at clinicaltrials.gov by September 1, 213 NCT I/II LAGE or NY-ESO-1 TCR no safety effectiveness / T-cell survival / ovarian cancer U-Penn T-cell function NCT13541 I/II NY-ESO-1 TCR yes safety / tolerability effectiveness / T-cell survival / melanoma U-Penn T-cell function NCT74938 terminated II p53 TCR, IL-2 yes effectiveness safety / T-cell survival kidney, melanoma, nonspecific metastatic cancer NCT7992 terminated II MART-1 TCR, +/- peptide vaccine, +/- no effectiveness / safety / t- not provided melanoma IL-2 cell survival NCT12222 terminated II MART-1 TCR, ALVAC MART-1 yes effectiveness safety / T-cell survival melanoma vaccine, IL-2 NCT1311 terminated II gp1 TCR, ALVAC gp1 vaccine, yes effectiveness safety / T-cell survival melanoma IL-2 NCT92339 terminated I/II 2G-1 (non-hla restricted) TCR, IL-2 yes effectiveness / safety safety / T-cell survival renal cancer NCT915 II MART-1 TCR, IL-2, DC vaccine yes effectiveness safety / feasibility / T-cell melanoma JCCC survival NCT I/II MAGE-A3/ (HLA-A1), NY-ESO-1 no safety / tolerability effectiveness myeloma (undergoing Adaptimmune TCRs autologous or syngeneic ) NCT I/II WT-1 TCR yes safety / transduction efficiency effectiveness AML, CML UCL NCT active, not I MAGE-A4 (HLA-A24) TCR, MAGE- A4 vaccine no effectiveness not provided NSCLC, melanoma, esophageal / head and neck carcinoma NCT39329 completed II p53 TCR, IL-2 yes safety / effectiveness T-cell survival melanoma, other metastatic cancers NCT59288 completed II MART-1 F5 TCR, IL-2 (PBL vs TIL) yes effectiveness safety / T-cell survival melanoma NCT5949 terminated II gp1 TCR, IL-2 (PBL vs TIL) yes effectiveness safety / T-cell survival melanoma NCT terminated I/II MAGE-A3/12 TCR, IL2 yes effectiveness not provided metastatic renal cancer, metastatic melanoma, other metastatic cancers NCT II NY-ESO-1 TCR, IL-2, DC vaccine yes effectiveness / safety / feasibility T-cell survival stage IV or locally advanced cancers TMUCIH JCCC Supplemental table 1 continued on next page

2 Supplemental table 1. Continued NCT9238 terminated I CEA TCR, IL-2 yes effectiveness / safety safety / T-cell survival metastatic cancers NCT completed II gp1 vs MART-1, IL-2, gp1 vs MART-1 vaccine yes effectiveness / t-cell survival safety melanoma NCT terminated I/II NY-ESO-1/IL-12 TCR yes safety / effectiveness T-cell survival renal cancer / melanoma / other metastatic cancers NCT7748 II NY-ESO-1 TCR, IL-2, +/- ALVAC yes effectiveness safety / T-cell survival renal cancer / melanoma / other NY-ESO-1 vaccine metastatic cancers NCT active, not I/II NY-ESO-1 and LAGE-1 TCR no safety / tolerability effectiveness myeloma Adaptimmune NCT1431 I/II HLA-A matched allogenic WT-1 TCR, IL-2 no safety /effectiveness effectiveness / T-cell survival CML, MDS, AML post allo FHCRC/UW CC NCT9114 completed I MART-1 TCR (PBL vs TIL) + MART- 1 vaccine + IL-2 yes safety / effectiveness effectiveness / T-cell survival melanoma NIHCC NCT15843 I TIL 1383I TCR, +/- IL-2 no safety / dose finding not provided melanoma LU ALVAC = Vaccine containing a canary pox virus; AML = acute myeloid leukemia; CML = chronic myeloid leukemia; DC = dendritic cell; EBV =Epstein Barr virus; JCCC = Jonsson Comprehensive Cancer Center; FHCRC/UWCC = Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium; LU = Loyola University; MDS = myelodysplastic syndrome; = National Cancer Institute; NIHCC = National Institutes of Health Clinical Center; NSCLC = non-small cell lung cancer; PBL = peripheral blood lymphocytes; TCR = T-cell receptor; = stem cell transplantation; TMUCIH = Tianjin Medical University Cancer Institute and Hospital; TIL = tumor-infiltrating lymphocytes; UCL = University College London, U-Penn = University of Pennsylvania.

3 Supplemental table 2. Overview of recent clinical phase I and II trials assessing the safety and efficacy of CAR-modified T-cells in cancer patients as registered at clinicaltrials.gov by September 1, 213 NCT793 3 NCT NCT827 NCT NCT NCT92432 NCT15939 NCT14339 NCT144 9 NCT1293 NCT987 NCT NCT NCT NCT NCT13114 NCT I CD19 CAR (2nd), EBV+ no safety effectiveness / T-cell survival NHL, CLL BCM I CD19 CAR (1st vs. 2nd) no safety effectiveness / T-cell survival NHL, CLL BCM I CD19 CAR (1st vs. 2nd) no safety effectiveness / T-cell survival NHL, CLL BCM I/II CD19 CAR, CMV, EBV, adenovirus+ no safety effectiveness / T-cell survival ALL, CLL, NHL pre or BCM / B-cell reconstitution post- I allo-cd19 CAR no safety effectiveness / T-cell survival B-cell malignancy relapsed post- I/II CD19 CAR, IL-2 yes safety / feasibility effectiveness / T-cell survival B-cell malignancy I CD19 CAR no safety / feasibility effectiveness / T-cell survival B-cell malignancy I CD19 CAR, allo-ebv no safety / T-cell survival effectiveness / T-cell survival ALL post- MSKCC I CD19 CAR (2nd 28 vs. 4 1BB) no safety effectiveness ALL MSKCC I CD19 CAR (1st vs. 2nd) no safety / feasibility effectiveness / T-cell survival B-cell malignancy U-Penn I CD19 CAR, ± IL-2 yes safety / feasibility not provided B-cell malignancy post- MDACC I CD19 CAR no safety / feasibility not provided B-cell malignancy postallo MDACC I/II CD19 CAR, CD8, Central Memory no safety effectiveness / T-cell survival B-cell malignancy post- CHMC I/II CD19 CAR/CMV+ or CD19 CAR EBV+ no safety / feasibility effectiveness / T-cell survival B-cell malignancy post- FHCRC I/II CD19 CAR (1st), EBV+, EBV-LCL no safety /effectiveness effectiveness / T-cell survival B-cell malignancy postallo UCL vaccine I CD3 CAR (2nd) no safety effectiveness / T-cell survival CD3+ NHL, HL BCM I CD3 CAR, EBV no safety effectiveness / T-cell survival CD3+ NHL, HL BCM Supplemental table 2 continued on next page

4 Supplemental table 2. Continued NCT88192 I kappa light chain CAR (2nd) no safety effectiveness / T-cell survival / B-cell reconsitution Kappa+ CLL, lymphoma or MM NCT21452 I CD2 CAR (3rd), IL-2 yes safety / feasibility effectiveness / T-cell survival B-cell malignancy FHCRC NCT11995 I/II Her2 CAR, CMV no safety / T-cell survival effectiveness / T-cell survival Her2+ glioblastoma BCM BCM NCT I Her2, TGFbeta dominant negative receptor (DNR) CAR, EBV no safety effectiveness / T-cell survival Her2+ lung cancer BCM NCT9244 I Her2 CAR (2nd) no safety effectiveness / T-cell survival Her2+ sarcoma BCM NCT8593 I GD2 CAR, EBV yes/no safety effectiveness / T-cell survival neuroblastoma BCM NCT419 I PSMA CAR yes safety effectiveness / PK / PD prostate cancer RWMC NCT73322 terminated I CEA CAR (2nd) no safety effectiveness / PK / PD colorectal cancer RWMC NCT completed I CEA CAR (2nd) no safety effectiveness / T-cell survival CEA+ liver metastases RWMC NCT73829 I CEA CAR (2nd), ± IL-2 no safety effectiveness / PK / PD breast cancer RWMC NCT4178 completed I CEA CAR no not provided not provived adenocarcinoma RWMC NCT1913 completed I folate receptor CAR, ± IL-2 no not provided not provived ovarian cancer NCT I/II EGFRvIII CAR (3rd), ± IL-2 yes safety / effectiveness effectiveness / T-cell survival glioblastoma NCT terminated I Her2 CAR (3rd), IL-2 yes safety / effectiveness T-cell survival metastasized Her2+ cancer NCT I PSMA CAR (2nd) yes safety / feasibility effectiveness / T-cell survival prostate cancer MSKCC NCT7313 completed I IL-13 zetakine CAR, Hy/TK suicide gene no safety / feasibility effectiveness / safety brain tumors CHMC NCT1491 I GD2 CAR multivirus specific no safety / T-cell survival T-cell survival / anti-infective Post-allo neuroblastoma CMHKC Supplemental table 2 continued on next page

5 Supplemental table 2. Continued NCT48 completed I CE7R CAR (1st),CD8, IL-2, Hy/TK suicide gene NCT active, not yet I CD19 CAR (2nd vs. 3rd) possible but not mandatory yes (individualized) not provided not provided neuroblastoma FHCRC safety effectiveness / T-cell survival NHL, CLL BCM NCT I mesothelin CAR no safety not provided pancreatic cancer ACCUP NCT18492 I/II CART-33 (1st vs 2nd) no safety effectiveness AML CPLAGH NCT18517 I/II CD19 CAR no safety / efficacy not provided B-cell malignancy FHCRC NCT active, not yet I GD2 CAR (3rd), icasp9 suicide gene no safety effectiveness / T-cell survival neuroblastoma BCM NCT18372 I emet CAR no safety not provided breast cancer ACCUP NCT17354 not CD2 CAR (2nd) no safety effectiveness B-cell Leuk/Lymph CPLAGH provided NCT not CD19 CAR (2nd), EBV+ no safety effectiveness B-cell Leuk/Lymph CPLAGH provided NCT18897 I/II CD138 CAR (2nd) no safety effectiveness myeloma CPLAGH NCT I CD19/ epidermal grow factor receptor no safety effectiveness / T-cell survival B-ALL SCH CAR NCT1845 I A, CD19 CAR yes safety Effetiveness NHL MSKCC NCT I A, CD19 CAR yes safety effectiveness NHL CHMC NCT12495 I CD19 CAR (1st vs 2nd) yes (individualized) safety effectiveness / T-cell survival B-cell Leuk/Lymph CHP NCT1891 I/II EGFR CAR (1st vs 2nd) no safety / T-cell survival effectiveness / T-cell survival EGFR+ solid tumors CPLAGH NCT II CD19 CAR (2nd), EBV+ no safety not provided CLL/SLL ACCUP NCT I CD19 CAR (2nd), EBV+ yes (individualized) safety not provided ALL ACCUP Supplemental table 2 continued on next page

6 Supplemental table 2. Continued NCT NCT17134 active, not yet I T1E28z CAR (intra-tumoral application) no safety / feasibility effectiveness / T-cell survival squamous cell cancer head/neck I Lewis Y CAR (2nd) no safety effectiveness / T-cell survival AML, MDS, myeloma PMCCC NCT18937 I CD19 CAR (2nd) yes/no safety T cell survival / B cell B-ALL MSKCC reconstitution NCT active, not yet I FAP CAR/CD8+ (intrapleural) yes safety not provided mesothelioma ZU NCT17233 II CEA CAR (2nd), IL-2 no effectiveness Safety metastatic cancer RWMC NCT suspended I CD19 CAR (1st) yes safety / T-cell survival T-cell survival NHL CHNHSFT NCT terminated I CEA MFEz CAR, IL-2 yes safety / T-cell survival effectiveness / T-cell survival solid tumors CRUK KCL NCT I mesothelin CAR (2nd) (mrna) no safety effectiveness mesothelioma ACCUP 1st = First generation CAR; 2nd = second generation CAR; 3rd = third generation CAR; ACCUP = Abramson Cancer Center of the University of Pennsylvania; ALL = acute lymphoblastic leukemia; AML = acute myeloid leukemia; BCM = Baylor College of Medicine; CAR = chimeric antigen receptor; CLL = chronic lymphocytic leukemia; CHMC = City of Hope Medical Center; CHNHSFT = Christie Hospital NHS Foundation Trust; CMHKC = Children s Mercy Hospital Kansas City; CMV = cytomegalovirus; CPLAGH = Chinese PLA General Hospital; CRUK = Cancer Research UK; EBV = Epstein Barr virus; FHCRC = Fred Hutchinson Cancer Research Center; HL = Hodgkin s lymphoma; KCL = King s College London; MDACC =MD Anderson Cancer Center; MDS = myelodysplastic syndrome; MM = multiple myeloma; MSKCC = Memorial Sloan-Kettering Cancer Center; NHL = non- Hodgkin s lymphoma; = National Cancer Institute; PMCCC = Peter MacCallum Cancer Centre, Australia; RWMC = Roger Williams Medical Center; SCH = Seattle Children s Hospital; = stem cell transplantation; SLL = small lymphocytic lymphoma; U-Penn = University of Pennsylvania; UCL = University College London; ZU = University of Zurich.

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