Mechanism of Action

BESPONSA is the first and only FDA-approved, CD22-directed, antibody-drug conjugate (ADC)2

The importance of CD22 as a therapeutic target in ALL2-8

  • Widely expressed–present in more than 90% of patients with B-cell ALL
  • Rapidly internalized by cells upon binding of the ADC
  • Highly specific B-lineage surface antigen–not expressed on hematopoietic stem cells or T cells

BESPONSA combines the specificity of an anti-CD22 humanized monoclonal antibody with the potent antitumor activity of calicheamicin2,7

Nonclinical data suggest BESPONSA delivers calicheamicin to CD22-expressing cells, inducing DNA damage and apoptosis2,7

  • The correlation between nonclinical data and clinical outcomes is unknown

1. BESPONSA binds preferentially to CD22
    on the surface of leukemic blasts.

3. The linker is cleaved inside the cell,
     allowing calicheamicin to enter the nucleus.

2. The BESPONSA-bound CD22 antigen is
     internalized by the cell.

4. Inside the nucleus, calicheamicin induces
    double-strand DNA breaks that result in
    apoptosis.

1. BESPONSA binds preferentially to CD22
    on the surface of leukemic blasts.

2. The BESPONSA-bound CD22 antigen is
     internalized by the cell.

3. The linker is cleaved inside the cell,
     allowing calicheamicin to enter the nucleus.

4. Inside the nucleus, calicheamicin induces
    double-strand DNA breaks that result in
    apoptosis.

ALL=acute lymphoblastic leukemia; DNA=deoxyribonucleic acid.

References
  1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Acute Lymphoblastic Leukemia V.1.2020. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed February 26, 2020. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content or its use or application and disclaims any responsibility for its use or application in any way.
  2. BESPONSA Prescribing Information. New York, NY: Pfizer Inc.
  3. Kantarjian HM, DeAngelo DJ, Stelljes M, et al. lnotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia. N Engl J Med. 2016;375(8):740-753.
  4. Shah NN, Stevenson MS, Yuan CM, et al. Characterization of CD22 expression in acute lymphoblastic leukemia. Pediatr Blood Cancer. 2015;62(6):964-969.
  5. Piccaluga PP, Arpinati M, Candoni A, et al. Surface antigens analysis reveals significant expression of candidate targets for immunotherapy in adult acute lymphoid leukemia. Leuk Lymphoma. 2011;52(2):325-327.
  6. Du X, Beers R, FitzGerald DJ, Pastan I. Differential cellular internalization of anti-CD19 and -CD22 immunotoxins results in different cytotoxic activity. Cancer Res. 2008;68(15):6300-6305.
  7. Shor B, Gerber H-P, Sopra P. Preclinical and clinical development of inotuzumab-ozogamicin in hematological malignancies. Mol Immunol. 2015;67(2 Pt A):107-116.
  8. Janossy G, Coustan-Smith E, Campana D. The reliability of cytoplasmic CD3 and CD22 antigen expression in the immunodiagnosis of acute leukemia: a study of 500 cases. Leukemia. 1989;3(3):170-181.