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Monoclonal antibody therapies in leukemias
1Division of Hematology-Oncology, Northwestern University Medical School, Robert H Lurie Comprehensive Cancer Center, Chicago, IL 60611, USA.
Abstract:
Significant advances in the development of monoclonal antibodies (unconjugated) and monoclonal antibodies conjugated to potent toxins or cytotoxic agents (immunoconjugates) have enabled improved targeting of leukemic cells with acceptable toxicities. Gemtuzumab ozogamicin, a calicheamicin-conjugated anti-CD33 monoclonal antibody, has demonstrated substantial efficacy in patients with acute myeloid leukemia (AML) and has induced remissions in patients with favorable-, intermediate-, and poor-risk cytogenetics. The immunoconjugate BL-22, comprised of an anti-CD22 monoclonal antibody fused to a fragment of pseudomonas exotoxin PE38, has produced high response rates in patients with purine analog-resistant hairy cell leukemia. Campath-1H (Wellcome, Beckenham, UK, and Ilex Oncology, San Antonio, TX), an anti-CD52 monoclonal antibody, has demonstrated significant activity in patients with previously untreated, relapsed, or refractory chronic lymphocytic leukemia (CLL), as well as in patients with T-cell prolymphocytic leukemia. The anti-CD20 monoclonal antibody rituximab also is effective in treating CLL and is being evaluated in combination with chemotherapeutic agents (cyclophosphamide) and fludarabine. Monoclonal antibodies may sensitize cells to chemotherapy. The optimal role of targeted therapy with monoclonal antibodies and immunoconjugates in acute and chronic leukemias has not yet been determined, but these novel therapies are beginning to fulfill their promise.
Insights
Monoclonal antibodies and immunoconjugates show promise in targeting leukemia cells. These targeted therapies, including gemtuzumab ozogamicin and rituximab, are demonstrating efficacy in various leukemia types.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Monoclonal antibodies (unconjugated) and immunoconjugates offer improved targeting of leukemic cells.
- These therapies have shown acceptable toxicity profiles.
Purpose of the Study:
- To review the efficacy of monoclonal antibodies and immunoconjugates in treating acute and chronic leukemias.
- To highlight advancements in targeted therapy for leukemia.
Main Methods:
- Review of clinical data on monoclonal antibodies and immunoconjugates.
- Analysis of specific agents like gemtuzumab ozogamicin, BL-22, Campath-1H, and rituximab.
Main Results:
- Gemtuzumab ozogamicin shows efficacy in acute myeloid leukemia (AML).
- BL-22 yields high response rates in hairy cell leukemia.
- Campath-1H and rituximab are effective in chronic lymphocytic leukemia (CLL).
Conclusions:
- Monoclonal antibodies and immunoconjugates are effective in treating various leukemias.
- These targeted therapies are beginning to fulfill their therapeutic potential.
- Further research is needed to determine the optimal role of these agents.