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For ALPN's tech [1], approaches include:

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jondoeuk   Sunday, 11/22/20 03:38:15 PM
Re: jondoeuk post# 113
Post # of 132 
For ALPN's tech [1], approaches include:

TIP(s): expression of a costimulatory vIgD ((novel) variant Ig domain), such as a CD86, on the surface of an engineered T-cell product would provide additional costimulation in a cis and/or trans fashion.

Decoy TIP(s)*: expression of a checkpoint, such as a PD-1 vlgD, on the surface of an engineered T-cell product, and in the absence of the normal inhibitory intracelluar domain, would compete with checkpoint ligands in the tumour microenvironment, and due to the high affinity, block any negative downstream effects.

Switch TIP: expression of a checkpoint, such as a PD-1 vIgD, on the surface of an an engineered T-cell product in association with an activating intracellular domain (CD28, 4-1BB and/or ICOS), turns a negative checkpoint signal into a T-cell activating (expansion and/or persistence) signal.

SIP(s)*: expression of secreted checkpoints, such as a PD-(L)1 vIgD, by an engineered T-cell product, would compete with checkpoint ligands in the tumour microenvironment, and modulate it, by being locally delivered.

The company has observed highly encouraging in vitro data with such approaches, where vIgDs enhance the proliferation, cytokine production, and cytotoxicity of engineered T-cell products [2].

Refs:
1 https://www.globenewswire.com/news-release/2019/05/15/1825189/0/en/Adaptimmune-and-Alpine-Immune-Sciences-Announce-Collaboration-and-License-Agreement-to-Develop-Next-Generation-SPEAR-T-Cell-Products.html
2 https://alpineimmunesciences.com/wp-content/uploads/2018/11/ALPN_ASH-2018_Switch-TIPs.pdf

* This would also reduce costs and toxicities associated with systemically given mAbs, such as Keytruda.

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