Table 2.
Overview of strategies for enhancing the efficacy of antibody-based therapies
| Agents | Strategy | Cancers | Reference | |
|---|---|---|---|---|
| 1. | Anti-MICAL-1 antibodies | Reactivating NK cell function | Melanoma | 66 |
| 2. | Cytokines IL-2 and IL-15 | Reactivating NK cell function | Head and Neck cancer | 112, 116 |
| 3. | Anti-KIR Antibody (Lirilumab) in combination with ICB | Reactivating NK cell function | Solid tumors (advanced and refractory) |
NCT01714739, NCT01750580 |
| 4. | IL-15 in Combination with ICB | Activation of immune system | Solid tumors (refractory) |
NCT03388632 |
| 5. | Anti-CD40 agonist antibodies (ChiLob7/4) Anti-CD40 plus Tremelimumab |
Direct cytotoxic effects on tumor cells Reprogramming of APCs |
Solid tumors Melanoma |
24 NCT01103635 |
| 6. | Anti-CSF-1 antibody (PD0360324/Lacnotuzumab) Anti-CSF-1R antibody (Emactuzumab/Cabiralizumab/ SNDX-6352) |
Sensitization to ICB via decreased infiltration of macrophages and MDSCs | PC, BC, Melanoma, Ovarian, malignant neoplasms, RCC, NSCLC, Billiary tract cancer | 70 |
| 7. | Antibodies against CD47-SIRPα axis | Acquired vasculogenic ability by the macrophages in the TME Enhanced trogoptosis by neutrophils |
Solid tumors | 15, 114, 117 |
| 8. | CXCR2 inhibition in combination with ICB antibodies | Inhibit trafficking of MDSCs to tumor site | Pediatric sarcomas | 69 |
| 9. | IL-2 in combination with anti-CTLA4 antibody | Expansion and differentiation of effector T cells | Melanoma | NCT01480323 |
| 10. | Anti-CD39/CD-73 antibodies in combination with ICB | Reversal of adenosine mediated T cell exhaustion | Solid tumors | 115 |
| 11. | Anti-VEGF/VEGFR2 antibody in combination with ICB | Vascular normalization, high endothelial venules (HEVs) formation, immune stimulation and decreased recruitment of immunosuppressive Tregs | PC, BC, CRC | 118, 119 |
Notes: This table summarizes the list of strategies being used to normalize tumor vasculature, decrease tumor-suppressive myeloid cells, and enhancing the cytotoxic activity of antibodies. PC, Pancreatic cancer; BC, Breast cancer; CRC, Colorectal cancer; RCC, Renal Cell Carcinoma; NSCLC, Non-small-cell lung carcinoma; IL-2, Interleukin-2; IL-15, Interleukin-15; NK, Natural Killer; DC, Dendritic cells; ADCC, Antibody-dependent cell cytotoxicity; ICB, Immune checkpoint blockade; APC, Antigen-presenting cell; MDSCs, Myeloid-derived suppressor cells; TME, Tumor microenvironment; CSF-1R, colony-stimulating factor receptor-1, CSF-1, colony stimulating factor-1; KIR, killer immunoglobulin receptor.