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Investigational CD33-targeted therapeutics for acute myeloid leukemia

Roland B Walter1,2,3

  • 1a Clinical Research Division , Fred Hutchinson Cancer Research Center , Seattle , WA , USA.

Expert Opinion on Investigational Drugs
|March 15, 2018
PubMed
Abstract

Insights

New antibody-drug conjugates and other CD33-targeted therapies show promise for acute myeloid leukemia (AML). While gemtuzumab ozogamicin (GO) is approved, ongoing research explores novel treatments for AML.

Area of Science:

  • Oncology
  • Hematology
  • Immunotherapy

Background:

  • Myeloid differentiation antigen CD33 is a validated target in acute myeloid leukemia (AML).
  • The antibody-drug conjugate (ADC) gemtuzumab ozogamicin (GO) has demonstrated efficacy in AML.
  • Several novel CD33-targeted therapeutics are under investigation, building on the success of GO.

Purpose of the Study:

  • To review the landscape of CD33-targeted therapeutics currently in clinical development for AML.
  • To discuss the progress and challenges associated with these novel agents.
  • To provide an outlook on the future of CD33-directed therapies in AML treatment.

Main Methods:

  • Review of clinical development status for various CD33-targeted agents.
  • Analysis of available clinical data, including efficacy and toxicity.
  • Discussion of the impact of gemtuzumab ozogamicin's re-approval on new drug development.

Main Results:

  • Multiple therapeutic modalities targeting CD33 are in early-phase clinical trials, including ADCs, unconjugated antibodies, radioimmunoconjugates, bispecific antibodies, and CAR-modified cells.
  • Vadastuximab talirine (SGN-CD33A), an ADC, has shown single-agent activity and encouraging results in combination therapy, but development is hindered by toxicity concerns.
  • Limited data exist for other agents, with early results for a new generation of CD33-targeted therapeutics anticipated soon.

Conclusions:

  • The development of CD33-targeted therapeutics for AML is a dynamic field with diverse approaches.
  • Toxicity remains a critical consideration, as exemplified by the challenges faced by SGN-CD33A.
  • The re-approval of gemtuzumab ozogamicin presents both validation and a higher bar for new CD33-targeted agents in AML.
Keywords:
Acute myeloid leukemia (AML)CD33adoptive immunotherapyantibodyantibody–drug conjugatebispecific antibodychimeric antigen receptorimmunotoxinradioimmunotherapytrispecific antibody

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