Table 3.

Overview of immunotherapy used against acute lymphoblastic leukemia.

Applied in clinics (BCP-ALL)
Type of Immunotherapy	Drug/Therapy Name	Mechanism of Action	References/ Clinical Trial No.
HSCT		Infusion of hematopoietic stem/progenitor cells	[40]
mAbs	Blinatumomab	Anti-CD19/CD3 bi-specific T-cell-mAb, which binds simultaneously to CD3-positive cytotoxic T cells and to CD19-positive B cells; endogenous T cells recognize and eliminate CD19-positive ALL blasts	[41] NCT02013167 NCT03628053
	Rituximab	Humanized murine mAb targeting CD20 on BCP-ALL cells	[42]
	Ofatumumab	Second-generation anti-CD20 mAb. Binds to a different epitope on the CD20 than Rituximab.	[43]
ADC (antibody-drug conjugates)	Inotuzumab ozogamycin	Humanized anti-CD22 antibody conjugated to a calicheamicin (cytotoxic drug); the CD22–conjugated complex is rapidly internalized and calicheamicin is released, which induces DNA double strand breaks	[44]
CAR-T cells	Tisagenlecleucel	Chimeric antigen receptor (CAR) T-cells targeting CD19 antigen and containing 4-1BB zeta co-stimulatory domain	[45] NCT03123939
Tested in clinical trials (BCP-ALL)
mAbs	Epratuzumab	Humanized anti-CD22 mAb (IgG1)	[46] NCT02844530 NCT01354457 NCT01802814
	Alemtuzumab	Fully humanized anti-CD52 mAb	[47,48]
	Blinatumomab + Nivolumab +/− Ipilimumab	Anti-CD19/CD3 bi-specific T-cell-mAb + Humanized anti-PD-1 mAb +/− Humanized anti-CTLA4 mAb	NCT02879695
	Blinatumomab +Nivolumab	Anti-CD19/CD3 bi-specific T-cell-mAb + Humanized anti-PD-1 mAb	NCT04546399
	Blinatumomab + Pembrolizumab	Humanized anti-PD-1 mAb	NCT03160079
	TTI-621 + Rituximab/Nivolumab	TTI-621 (SIRPαFc) is a soluble recombinant fusion protein composed of the N-terminal CD47 binding domain of human SIRPα and the Fc domain of human immunoglobulin (IgG1); TTI-621 binds to CD47 and prevents “do not eat” (anti- phagocytic) signaling	NCT02663518
ADC	Denintuzumab	Humanized anti-CD19 antibody conjugated to a microtubule-disrupting agent monomethyl auristatin F (MMAF)	[49]
	Coltuximab ravtansine (SAR3419)	Anti-CD19 monoclonal antibody conjugated to potent inhibitor of tubulin polymerization and microtubule assembly, maytansinoid, DM4	[50]
CAR-T cells	CD19-CD22 CAR-T	Modified autologous T cells expressing anti-CD19 and anti-CD22 CARs	[39] NCT04626765
	CD22 CAR-T	Modified autologous T cells expressing anti-CD22 CARs	[39] NCT04626765
	CD19–28z CAR-T	Modified autologous T cells expressing anti-CD19 CARs with CD28 co-stimulatory domain	[39]
NK cells	Allogenic activated NK cells	Infusion of IL-15/IL-21-activated NK cells after HLA-mismatched HSCT	[51]
	Allogenic activated NK cells	Activated and expanded natural killer cells (NKAEs) from haploidentical donor infused to patients	NCT02074657
	Autologous NK cells	Enriched and expanded autologous NK cells	NCT02185781
	Cord blood NK cells	Personalized cord blood (CB)-derived NK cells for HLA-C2/C2 patients after chemotherapy	NCT02727803
	Cord blood NK cells	CD19-CD28-zeta-2A-iCasp9-IL15-transduced cord blood natural killer (CB-NK) cells recognizing CD19+ tumor cells	NCT03056339
Tested in clinical trials (T-ALL)
mAbs	Isatuximab	Anti-CD38 mAb	NCT02999633 NCT03860844
	Daratumumab	Anti-CD38 mAb	NCT03384654
	Alemtuzumab	Anti-CD52 mAb	NCT00199030 NCT00061048 NCT00061945
CAR-T cells	CD4 CAR-T	Modified T cells expressing anti-CD4 CARs	NCT03829540 NCT04162340
	CD5 CAR-T	Modified T cells expressing anti-CD5 CARs	NCT03081910
	CD7 CAR-T	Modified T cells expressing anti-CD7 CARs	NCT04004637 NCT04264078 NCT03690011 NCT04033302 NCT04480788
NK cells	CD7 CAR NK cells	Modified NK cells expressing anti-CD7 CARs	NCT02742727

Abbreviations: ADC, antibody-drug conjugates; Casp9, caspase 9; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; HSCT, hematopoietic stem-cell transplantation; mAbs, monoclonal antibodies; PD-1, programmed death receptor 1; SIRPαFc, signal regulatory protein α fragment crystallizable.