Biological therapy for pediatric malignancy: Current perspectives

Abstract

Biologicals are defined as agents that are either uniquely or partially tumor-specific. Great expectations were raised by the success in agents that target a specific genetic translocation: all-trans retinoic acid, targeting the chronic myeloid leukemia retinoic acid receptor in acute promyelocytic leukemia and imatinib, a small molecule targeting the BCR-ABL translocation in chronic myeloid leukemia (CML). Thus far, the search for similar "druggable" genetic targets in pediatric cancers has not yet resulted in such dramatic results. The rarity of pediatric cancer as well as ethical considerations necessitate that the agents for testing be carefully and rigorously selected. Biologicals present an additional challenge, as they often do not lend themselves to in vitro testing. Early approaches to specific targeting of solid tumors utilized monoclonal antibodies. The microenvironment provides an interesting new biological approach to treating tumors and alteration of the host immune response provides another avenue. Biological agents are a step forward in supportive care to reduce the hematological toxicity of high-dose chemotherapy and to manage the frequent infectious complications.

Pediatric Cancer: A Comprehensive Review. Part II: Chemotherapy, Monoclonal Antibodies and Tyrosine Kinase Inhibitors

“…Other technologies, such as cancer vaccines, antisense oligonucleotides and small-interfering RNAs (siRNAs) are being studied but have not yet made it to clinical practice. 6…”

“…The human immune system recognizes murine antibodies as foreign, rapidly removing them from the circulation and causing systemic inflammatory effects (hypersensitivity reactions). [5][6][7][8][9][10][11] A solution to this problem would be to generate human antibodies directly from humans. However, this is not easy, primarily because it is generally not seen as ethical to challenge humans with antigen in order to produce antibody; the ethics of doing the same to non-humans is a matter of debate.…”

“…Another approach involves using mice genetically engineered to produce antibodies that are more humanlike. 5,6,[8][9][10][11] Monoclonal antibody drugs There are several mAbs, some in combination with small molecules and other agents, that are being studied for use in the treatment of pediatric cancer. None of these agents are currently licensed for use in the treatment of pediatric cancers in North America.…”

“…CD22 is widely expressed in B-cell lymphomas and B-precursor ALL. 5,6,[8][9][10][11] This agent may prove to be effective in combination with chemotherapy in treating children with lymphoma and leukemia.…”

“…Bevacizumab is an antiangiogenesis agent approved for the treatment of colon cancer in adults and has shown activity in carcinoma of the kidney, adenocarcinoma of the rectum and non-small-cell lung cancer. 5,6,[8][9][10][11] VEGF is overexpressed in a number of solid tumours seen in children, including Ewing sarcoma and glioblastomas, and is currently being investigated in these and other pediatric solid tumours.…”