|CAR T cell therapy||Target antigen||Malignancy||CAR expression technology||Gene editing strategy to mitigate negative alloreactivity factors||Efficacy||CAR T cell expansion and persistence||Toxicities||Phase||References|
|CD19||r/r B-ALL, r/r NHL||Lentiviral transduction of CAR19 construct into activated CD4 and CD8 enriched T cells derived from autologous PBMCs in leukapheresis product.||Not applicable||
Phase I: Overall 40/45 (89%) MRD– CR remission rate; 93% MRD– CR in CAR T-treated patients and 100% in patients who also had fludarabine and cyclophosphamide lymphodepletion.|
Phase II: Anti-tumor response in 5/6 patients at 3 weeks, with CR by Week 9 in 2 DLBCL patients but not sustained despite CAR T persistence; 1 CR patient developed new CD19+ site at 6 months but CR at 3 weeks post second CAR T infusion; 1 PR patient developed CD19– at 9 weeks.
Phase I: Functional CAR T persistence until CD19– relapse 8 months post-infusion.|
Phase II: All patients showed CAR T cell expansion in PB, BM, and CSF with ongoing persistence at 14 days to 9 months.
Phase I: Reversible severe CRS and/or reversible severe neurotoxicity in 23% patients; no patient deaths from toxicity.|
Phase II: CRS: Grade I (n = 3), Grade II CRS (n = 1), Grade III CRS (n = 1). Neurotoxicity: Grade I (n = 1), Grade 2 (n = 1), no severe neurotoxicity.
45 children and young adults
8 patients (4–18 yrs): r/r DLBCL (n = 4), Burkitt's lymphoma (n = 2), gray zone B cell lymphoma (n = 1), primary mediastinal B cell lymphoma (n = 1)
Gardner et al. (2017) 
Rivers et al
|BCMA||r/r MM||Non-viral piggyBac transposon delivers anti-BCMA CAR (fused with the less immunogenic Centyrin protein to CD3ζ/4-1BB) with a safety switch to autologous T cells harvested from leukapheresis, while retaining high %TSCM||Not applicable||57% ORR for 34 patients treated with single P-BCMA-101 during initial dose escalation; 4 patients treated with cyclic P-BCMA-101, rituximab, lenalidomide, or single P-BCMA-101 at lowest dose showed 100% ORR with ongoing responses and minimal CRS.||Patients treated with rituximab or lenalidomide pre- and post-lymphodepletion showed gradual TSCM expansion (peak at 2–3 weeks and detectable for up to 1.5 years) and increased T cell robustness.||CRS in 17% patients: Grade III in 1 patient, neurotoxicity in 1 patient, 3 patients treated with tocilizumab, no patients admitted to ICU admission or needed safety switch activation. No patient deaths or off-target toxicities. 79% Grade III neutropenia, 30% thrombocytopenia, 30% anemia.||
Phase I/II (PRIME):|
43 patients (67% male, 33% female, median age 60 yrs)
Costello et al. (2019–2021) [54,55,56]
|CD19||r/r B-ALL||Recombinant lentiviral transduction of CAR19 (4-1BB) with CD20 target mimotope for rituximab (safety switch) into healthy donor T cells.||TRAC and CD52 KO using mRNA encoding TALENs to disrupt TCRαβ expression to limit GVHD, while making the CAR T cells resistant to anti-CD52 monoclonal antibody lymphodepletion.||14/21 (67%) patients with CR or CR with incomplete hematological recovery 28 days post-infusion; patients (n = 4) not given alemtuzumab showed no UCART19 expansion or anti-leukemic activity; median duration of response 4.1 months with 10/14 (71%) responders proceeding to allo-SCT; progression-free survival 27% at 6 months; overall survival 55%.||Rapid UCART19 expansion in blood with peak at Day 14 and reduction by Day 28 with persistence in some patients; 15/17 (88%) patients treated with fludarabine, cyclophosphamide, and alemtuzumab showed UCART19 expansion; no UCART19 expansion in patients treated with only fludarabine and cyclophosphamide but showed indications of earlier host lymphocyte recovery; larger AUC for first 28 days post-UCART19 in responders than non-responders; UCART19 persisted past Day 42 in 3 patients with 1 patient showing detectable UCART19 at Day 120.||CRS in 19 patients (91%); Grade III–IV CRS in 3 patients (14%); neurotoxicity in 8 patients (38%); Grade I acute skin GVHD in 2 patients (10%); Grade IV prolonged cytopenia in 6 patients (32%); 1 death from neutropenic sepsis with concurrent CRS; 1 death from pulmonary hemorrhage with persistent cytopenia.||
Phase I (PALL):|
Phase I (CALM):
Benjamin et al. (2020) 
|CD19||r/r DLBCL, LBCL, Grade 3B FL||CAR19 transgene construct inserted into TRAC locus of donor T cells using multiplex CRISPR-Cas9 editing (no lentivirus or retrovirus).||CRISPR-Cas9 mediated TRAC KO to disrupt TCR expression to mitigate GVHD, and B2M KO to disrupt β-microglobulin and remove MHC-I expression to limit rejection and enhance CAR T cell persistence.||Single CTX110 dose at level 2+ (intent-to-treat) achieved 58% ORR and 38% CR rate in LBCL; CR rate 21% at 6 months; 4/9 patients achieved CR at Day 28 and stayed in CR at 6 months (remaining 5 patients not reached 6-month evaluation yet); longest response rate at 18 months.||CTX110 expansion or persistence kinetics not yet reported.||No GVHD; only Grade I–II CRS and resolved with standard management; CTX110 re-dose did not increase CRS frequency or severity; Grade III+ ICANS in 1 patient with concurrent HHV-6 encephalitis; no ICANS at dose levels 3–4; 1 patient with pseudomonal sepsis (resolved in 4 days).||Phase I (CARBON): recruiting; treated 29 adult patients so far||
McGuirk et al. (2021) 
CRISPR Therapeutics (2021)