Table 1.
Similarities and differences between CIK cells, CAR-T cells and BiTEs in lymphoma.
| CIK Cells | CAR-T Cells | BiTEs | |
|---|---|---|---|
| Manufacturing Process | PBMCs sequentially activated with 1000 IU/m IFN-γ on day 0, and 50 ng/mL anti-CD3 mAb and 600 IU/mL IL-2 on the following day; IL-2 supplemented every 2–3 days | T cells with CAR gene transduction primarily by lentiviruses; CARs consist of an scFv based ectodomain for antigen-binding, a transmembrane domain, and an endodomain containing TCR CD3ζ chain with or without costimulatory signaling components | Antibodies designed to bind to a selected TAA and CD3 on T cells simultaneously; produced in bioreactors by mammalian cell lines as secreted polypeptides |
| Effector Cells | CD3+CD56+ cells | Mostly αβ-TCR+ T cells | Endogenous CD8+ or CD4+ T cells |
| Cell Source | Autologous/allogeneic | Autologous/allogeneic | Autologous |
| Target Antigen | MIC A/B and ULBP1–4 | CD19, CD20, CD22, CD30, BCMA, etc. | CD19 |
| MHC Restriction | Dual-functional capability (non-MHC-restricted and TCR-mediated lysis) | TAA recognition by CARs is MHC-unrestricted | MHC-unrestricted |
| Mechanism | Release of perforin and granzyme B from CIK cells | Release of perforin and granzyme B from CAR-T cells | Activating T cells to release perforin and granzyme B by linking TAAs to CD3 on T cells |
| Toxicities and Side effects | Low-grade toxicities including fever, chills, fatigue, headache, and skin rash; grade 3 and 4 toxicities are rare; limited GVHD response in the allogeneic setting | CRS, ICANS, and MAS/HLH; potentially life-threatening | CRS and ICANS; severe toxicities are one of the major concerns |
| Clinical Efficacy | Varied due to heterogeneity of expension method and study design | Axicabtagene ciloleucel: 83% ORR, 58% CR; Tisagenlecleucel: 54% ORR, 40% CR; Lisocabtagene maraleucel: 73% ORR, 53% CR [27,28,29] | Blinatumomab: 36% to 69% ORR in relapsed/refractory NHL [11,30] |
CIK cells, cytokine-induced killer cells; MIC A/B, MHC class I-related molecules A and B; ULBP1–4, UL16-binding protein; GVHD, graft-versus-host diseases; CAR, chimeric antigen receptors; scFv, single-chain variable fragment; TCR, T cell receptor; TAA, tumor-associated antigen; CRS, cytokine release syndrome; ICANS, immune effector cell-associated neurotoxicity syndrome; MAS/HLH, Macrophage activation syndrome/hemophagocytic lymphohistiocytosis; CR, complete remission; ORR, objective response rate; BiTE, bispecific T cell engager.