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Review
. 2021 Jun 8;13(12):2853.
doi: 10.3390/cancers13122853.

Bispecific T Cell Engagers for the Treatment of Multiple Myeloma: Achievements and Challenges

Kinan Alhallak  1   2 , Jennifer Sun  1   2 , Amanda Jeske  1   2 , Chaelee Park  1 , Jessica Yavner  1 , Hannah Bash  1 , Berit Lubben  1 , Ola Adebayo  1 , Ayah Khaskiah  3 , Abdel Kareem Azab  1   2
Affiliations
Review

Bispecific T Cell Engagers for the Treatment of Multiple Myeloma: Achievements and Challenges

Kinan Alhallak et al. Cancers (Basel). .

Abstract

MM is the second most common hematological malignancy and represents approximately 20% of deaths from hematopoietic cancers. The advent of novel agents has changed the therapeutic landscape of MM treatment; however, MM remains incurable. T cell-based immunotherapy such as BTCEs is a promising modality for the treatment of MM. This review article discusses the advancements and future directions of BTCE treatments for MM.

Keywords: bispecific T cell engagers; chimeric antigen receptor-T cells; multiple myeloma.

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Conflict of interest statement

A.K.A. and K.A. have filed a patent with regards to the nanoBTCE technology described in this manuscript. Other authors state no conflict of interest.

Figures

Figure 1
Figure 1
Creation of the BTCE using scFvs of two monoclonal antibodies (mAbs) linked together using a protein linker. The anti-tumor associated antigen scFv specifically recognizes the desired TAA on the tumor cell while the anti-CD3 scFv recognizes the CD3 molecule on the T cell. This enables a highly specific and bivalent system for T cell-based immunotherapy.
Figure 2
Figure 2
Molecular mechanism of BTCE-induced T cell activation. (A) The kinetic-segregation model proposes that the exclusion of CD45 is a prerequisite for T cell activation. (B) As the antigen presenting cell (APC) gets in proximity of the T cell, CD45 is subsequently excluded and the peptide major histocompatibility complex (pMHC) interacts with the T cell receptor (TCR) and enables activation. (C) For BTCE-induced T cell activation, the BTCE brings the tumor cell in proximity of the T cell to exclude CD45 from the close-contact zone and enable subsequent T cell activation.
Figure 3
Figure 3
Mechanism of tumor escape and relapse after BTCE therapy targeting only one surface marker due to development of antigen-less clones.
See this image and copyright information in PMC

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