Mosunetuzumab

(RG7828)

CD20/TDB, an investigational, full-length, bispecific antibody
Breast
  • Phase
  • I
  • II
  • III
Gastrointestinal
  • Phase
  • I
  • II
  • III
Genitourinary
  • Phase
  • I
  • II
  • III
Gynecologic
  • Phase
  • I
  • II
  • III
Hematology
  • Phase
  • I
  • II
  • III
Lung
  • Phase
  • I
  • II
  • III
Melanoma
  • Phase
  • I
  • II
  • III
Solid Tumor
  • Phase
  • I
  • II
  • III

This compound and its uses are investigational and have not been approved by the US Food and Drug Administration. Efficacy and safety have not been established. The information presented should not be construed as a recommendation for use. The relevance of findings in preclinical studies to humans is currently being evaluated.

Mosunetuzumab, a T cell-dependent bispecific antibody

Mosunetuzumab is an investigational, humanized, T cell-dependent bispecific antibody designed to engage T cells and redirect their cytotoxic activity against malignant B cells. Mosunetuzumab simultaneously binds to CD3 epsilon (CD3ε), a component of the T-cell receptor (TCR) complex, and to CD20, a B-cell surface protein expressed in a majority of B-cell malignancies. This results in crosslinking of the TCR, inducing downstream signaling events that lead to B-cell killing.1-3

Mosunetuzumab is equipped with structural features that promote T-cell recruitment and retention, resulting in an antitumor effect.1,4 In preclinical models, mosunetuzumab induced T-cell proliferation and B-cell death; furthermore, efficient B-cell killing was achieved at low effector-to-target (T cell:B cell) ratios. 1 Use of mosunetuzumab in combination with PD-L1 inhibition may address adaptive immune resistance mechanisms to enhance anticancer activity against B-cell malignancies.4-6

 

1Mosunetuzumab is an investigational, full-length, bispecific antibody designed to simultaneously bind to CD20 on the surface of malignant B cells and to CD3ε on cytotoxic T cells, resulting in crosslinking of the TCR and subsequent formation of an immunologic synapse and T-cell activation.1,2,7

CD20/TDB is designed to simultaneously bind to CD20 on malignant B cells and to CD3ε on T cells

 

2T cells are activated through a cascade of downstream signaling events, leading to the secretion of cytotoxic granules and B-cell death. T-cell activation promotes the proliferation/expansion of pre-existing T cells, which may further contribute to the depletion of B cells.1,2,8

T-cell activation leads to the secretion of cytotoxic granules and B-cell death

 

3 In preclinical models, mosunetuzumab induced T-cell activation and proliferation, as well as B-cell death.Mosunetuzumab continues to be investigated in an ongoing clinical study, including in combination with PD-L1 inhibition for the treatment of B-cell malignancies.9

CD20/TDB induced T-cell activation and proliferation, as well as malignant B-cell death

References

  1. Sun LL, Ellerman D, Mathieu M, et al. Sci Transl Med. 2015;7:287ra70. PMID: 25972002
  2. Bacac M, Klein C, Umana P. Oncoimmunology. 2016;5:e1203498. PMID: 27622073
  3. Prevodnik VK, Lavrenčak J, Horvat M, Novakovič BJ. Diagn Pathol. 2011;6:33. PMID: 21486448
  4. Sun LL, Wang P, Clark R, et al. Blood. 2016;128:4168.
  5. Kim JM, Chen DS. Ann Oncol. 2016;27:1492-1504. PMID: 27207108
  6. Tumeh PC, Harview CL, Yearley JH, et al. Nature. 2014;515:568-571. PMID: 25428505
  7. Dieckmann NMG, Frazer GL, Asano Y, Stinchcombe JC, Griffiths GM. J Cell Sci. 2016;129:2881-2886. PMID: 27505426
  8. Borroto A, Arellano I, Blanco R, et al. J Immunol. 2014;192:2042-2053. PMID: 24470497
  9. US National Institutes of Health. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02500407. Accessed March 9, 2018.