Table 2.
Current and most promising NK cell immunotherapies used in hematological cancers. ADCC, antibody-dependent cell-mediated cytotoxicity; CDC, complement-dependent cytotoxicity; HSCT, hematopoietic stem cell transplantation; CAR, chimeric antigen receptor CLL, chronic lymphocytic leukemia; AML, acute myeloid leukemia; GvHD, graft-versus host disease.
| Therapy | Features | Disadvantages | References |
|---|---|---|---|
| NK Cells Cell-Mediated ADCC | |||
| Rituximab | Clinical benefits in most B-cell lymphomas and CLL | Risk for hypersensitivity reactions | [63,64,65,66,67,68,69,70,71,72,73] |
| Obinutuzumab | Increases ADCC | Limited clinical experience | [67,68,69,70,71,72,73] |
| Ofatumumab | Increases CDC | Clinical relevance not established | [74,75] |
| Daratumumab | Induces ADCC and CDC | Role of NK cells not elucidated | [76,77,78,79] |
| Elotuzumab | Induces NK cell activity and ADCC | Anti-elotuzumab antibodies may limit efficacy | [80,81] |
| BiKEs/TRiKEs | Redirect NK cells | Limited clinical experience | [82,83,84,85] |
| HSCT and Adoptive Transfer | |||
| HSCT | Highly efficient in KIR-HLA mismatched patients. No risk of graft vs host disease (GvHD) | Efficacy only demonstrated in AML | [54,55,86,87,88,89,90,91,92,93,94,95,96,97] |
| Autologous/ Allogenic NK cells | Universal use. No risk of GvHD | Low persistence, activity and efficacy of NK cells | [98,99,100] |
| CAR-NK cells | Potent antitumor activity and safer than CAR-T cells | Difficult to manipulate, limited persistence and efficacy | [101,102,103,104,105,106,107] |
| Immunomodulatory Drugs | |||
| Lenalidomide | Induces NK cell activity and ADCC | Combination with dexamethasone may affect NK cells | [108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123] |
| Pomalidomide | Increases effectiveness | May induce inhibitory checkpoints expression on NK cells | [124,125] |
| Inhibitory Receptors | |||
| PD-1 and PD-L1 | Relevant results in patients with HL | Role of NK cells not elucidated | [126,127,128,129,130,131,132,133,134,135,136] |
| Lirilumab | Mimics missing-self scenario | Low clinical efficacy, needs combination | [137] |
| Monalizumab | Induces NK cell activity. Potential for combination with HSCT in AML | No clinical data available | [138,139,140,141,142,143] |
| Urelumab and Utomilumab | Induces NK cell activity and ADCC | High toxicity and/or low clinical efficacy as monotherapy | [144,145] |