Explore CD79b

CD79b, a component of the B-cell receptor (BCR), is expressed on over 90% of B-cell NHL malignancies.1,2

Genentech's successful experiences with researching B-cell antigens, such as CD20, has led to exploration of additional B-cell surface proteins.3,4 CD79b, along with CD79a and a surface immunoglobulin, make up the BCR. CD79b, like CD20, is expressed on nearly all B-cell surfaces.1,2,5

We are investigating novel approaches to utilize the unique features of CD79b to provide new options for patients with B-cell malignancies.6,7

CD79b: a B-cell surface antigen with unique functionality

CD79b can be internalized upon antibody binding, unlike other highly expressed B-cell surface antigens.3,8 Due to this unique functionality, CD79b has the potential to selectively deliver molecules of interest to B cells found in non-Hodgkin lymphomas (NHLs) such as diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL).5-7

CD79b-specific binding in B-cell malignancies

BCR Complex and CD79b image: BCR/CD79b complex and B-cell surface

CD79b, a component of BCR, is expressed on over 90% of B-cell NHL malignancies.1,2 Preclinical research has shown that select monoclonal antibodies can recognize and bind CD79b.3

Exploiting CD79b internalization

B-cell surface image: BCR/CD79b complex and B-cell internalization

In preclinical models, antibody binding to CD79b was shown to trigger the internalization of the BCR and bound antibody. This research established the potential for selective delivery of molecules of interest to B cells.3

Degrading the internalized antibody and BCR

B-cell environment image: BCR degradation inside B cell

Once internalized, the BCR complex and bound antibodies are degraded in acidic vacuoles.However, some molecular components evade degradation and diffuse into the intracellular environment.9

References

  1. Young RM, Shaffer AL, Phelan JD, Staudt LM. Semin Hematol. 2015;52:77-85. PMID: 25805587
  2. D’Arena G, Musto P, Cascavilla N, et al. Am J Hematol. 2000;64:275-281. PMID: 10911380
  3. Polson AG, Yu S-F, Elkins K, et al. Blood. 2007;110:616-623. PMID: 17374736
  4. Pfeifer M, Zheng B, Erdmann T, et al. Leukemia. 2015;29:1578-1586. PMID: 25708834
  5. Dornan D, Bennett F, Chen Y, et al. Blood. 2009;114:2721-2729. PMID: 19633198
  6. US National Institutes of Health. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02257567 Published October 6, 2014. Updated August 2, 2018. Accessed August 17, 2018.
  7. Roche third-quarter results 2018 presentation. https://www.roche.com/dam/jcr:f9cad8fc-8655-4692-9a85-efbe1cf7a59b/en/irp181017.pdf Published October 17, 2018. Accessed October 22, 2018.
  8. Caballero A, Katkere B, Wen XY, Drake L, Nashar TO, Drake JR. Eur J Immunol. 2006;36:3131-3145. PMID: 17125144
  9. Rock BM, Tometsko ME, Patel SK, et al. Drug Metab Dispos. 2015;43:1341-1344. PMID: 26101225

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