Pediatric cancers such as neuroblastoma and osteosarcoma are known to be very stubborn and difficult to cure. However, thanks to a research conducted by Stanford University - School of Medicine, a synergic scenario of two antibodies (anti-CD47 and anti-GD2) cured mice. In fact, neuroblastoma is a cancer common in children concerned with uncontrollable neuroblasts forming a solid tumor. On the other hand, osteosarcoma is a bone cancer starting from osteoblasts common in children, adolescents and young adults. Unfortunately, these two cancers are recalcitrant and most of the cases ends up with death due to no response to chemotherapy, surgery or radiation. Actually, that’s the case of one-third to one-half of patients.
Indeed, the two antibodies behind the cure are anti-GD2 and anti-CD47. To illustrate, the cancer cells has markers on their surfaces to each of the two antibodies. Usually cancer cells emits signals to avoid death by the immune cells, but when anti-GD2 and anti-CD47 binds to the cell, death is inevitable. Above all, when anti-CD2 alone or anti-CD47 alone binds the cancer cells, no positive results are met. Therefore, the treatment lies within the synergy of both antibodies.
In tumors, macrophages play a crucial role in immune defense, but tumors resist phagocytosis by expressing “don't eat me signals", induced by the checkpoint molecule CD4.
The mechanism behind the treatment:
1- The binding of anti-GD2 to cancer cell surface marker “GD2”:
- Upregulates Calreticulin on cell surface, which is an “eat me” pro-phagocytic signal
- Blocks the binding of GD2 to inhibitory immunoreceptor Siglec-7 (it’s ligand)
2- Blocks the binding of GD2 to inhibitory immunoreceptor Siglec-7 (it’s ligand)
Not only it acts on neuroblastoma, it also reduces small-cell lung cancer and enhance survival rate. To clarify, In osteosarcoma, the combination of antibodies had some limited efficacy, but the mice did not develop lung metastases. This is promising as lung metastases are a common death cause for patients with osteosarcoma.
-Theruvath J, Menard M, Smith BAH, et al. Anti-GD2 synergizes with CD47 blockade to mediate tumor eradication. Nat Med. 2022;28(2):333-344. doi:10.1038/s41591-021-01625-x