Mechanism of Action

BESPONSA is the first and only approved CD22-directed antibody-drug
conjugate (ADC)1,2

The importance of CD22 as a therapeutic target in ALL3-8

  • Widely expressed, present in over 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 calicheamicin1,7

Nonclinical data suggest BESPONSA delivers calicheamicin to CD22-expressing cells, inducing DNA damage and apoptosis1,7

  • 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.

References
  1. BESPONSA Prescribing Information. New York, NY: Pfizer Inc.
  2. National Cancer Institute. Drugs approved for leukemia. Cancer.gov website. http://www.cancer.gov/about-cancer/treatment/drugs/leukemia. Updated May 19, 2017. Accessed July 17, 2017.
  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.