Table 5 The advantages and limitations of various immunotherapies in hematologic malignancies

allo-HSCT

The only option to achieve a cure for hematologic malignancies.

Incidence of transplant related mortality and graft-versus-host disease.

Personalization and combination therapy; optimization of donor selection, maintenance therapy to balance the anti-GVHD and anti-tumor benefits.

mAb

Specifically targeting tumor antigen and inducing cancer cell death; their combination with chemotherapy has been first-line therapy for several cancers.

Incidence of “off tumor, on target” effect and therapy-related toxicities.

Requirement for suitable target antigen; optimization of treatment strategy; overcome drug resistance to single-agent therapies.

bsAb

Combining the binding sites of two monoclonal antibodies in the same one molecule to promote cancer cell killing.

Incidence of “off tumor, on target” effect and therapy-related toxicities; a lack of co-stimulation might induce T-cell anergy and compromise the clinical efficacy;

Requirement for suitable target antigen; need to selecting the best target combination; require rational structural design; optimization of treatment strategy; overcome drug resistance to single-agent therapies.

ADC

Utilizing the specific binding properties of mAb to selectively deliver cytotoxic agents to cancer cells to increase the therapeutic potentials of cytotoxic agents.

Incidence of “off tumor, on target” effect and therapy-related toxicities.

Requirement for suitable target antigen; require rational structural design; solve the complexity of pharmacokinetics, enhance drug stability, improve drug efficacy and reduce drug resistance; optimization of treatment strategy; design of bsADCs; overcome drug resistance to single-agent therapies.

ICI

Blockade of immunosuppressive checkpoint signaling pathway.

Incidence of irAEs; only the therapeutic results in HL was remarkable.

Overcome drug resistance to single-agent therapies; combination therapy with epi-drugs, CAR-T therapy and/or HSCT.

CIK, γδ T and NK cells

Non-specific cellular therapies; no demand for genetical modification.

Requirement for a large number of cells; limited efficacy in hematologic malignancies.

Improvement of clinical efficacy and reduction of toxicity; combination therapy with epi-drugs, ICIs and/or HSCT.

CAR-T cell therapy

Specific cellular therapies; no restriction of MHC; achieve rapid development and great success in treating hematologic malignancies, especially R/R patients; serve as the “bridge” to transplant; several cell products have achieved FDA’s approval and entered into the commercialized field.

Therapy-related toxicities, such as CRS and neurotoxicity; long period of manufacturing; high cost.

Requirement for suitable target antigen; optimization of CAR design and cell products; improvement of remission rates; prolongation of remission duration; reduction of toxicity and expansion of this therapeutic modality to other cancer types; universal CAR-T products; overcome drug resistance to monotherapy; combination therapy with epi-drugs, ICIs and/or HSCT.

CAR-NK cell therapy

Specific cellular therapies; no restriction of MHC; provide an “off-the-shelf” cell product and could be readily available for immediate clinical use; serve as the “bridge” to transplant.

Still in early stage of clinical studies; limited efficacy in hematologic malignancies.

Requirement for suitable target antigen; optimization of CAR design and cell products; improvement of clinical efficacy and reduction of toxicity; expansion of this therapeutic modality to other cancer types; overcome drug resistance to monotherapy; combination therapy with epi-drugs, ICIs and/or HSCT.

Tumor vaccine

Taking advantage of tumor-associated antigens or tumor-specific antigens to stimulate the immune system.

Still in very early stage of clinical study; limited efficacy in hematologic malignancies.

Requirement for suitable target antigen and vaccine vectors; improvement of clinical efficacy and reduction of toxicity.