Immune Checkpoints (IC)
Co-inhibitory and co-stimulatory immune checkpoint signaling
Over the last decade, the understanding of the regulation of T cell responses has led to the groundbreaking, and Nobel prize-winning, development of immune checkpoint (IC) blockade which has revolutionized cancer treatment [1]. Dysregulated checkpoints can lead to excessive immune responses (i.e. autoimmune diseases) [2], or immuno‑suppressive conditions (i.e. cancers) [3]. Currently, there are numerous co‑inhibitory and co‑stimulatory ICs found on the different cells that populate the tumor microenvironment (TME) under investigation. Novel immunotherapeutic approaches target these ICs as levers for action, either blocking or enhancing their inhibitory or stimulatory functions, respectively [4-6].
Immune Checkpoint Product Collection
InvivoGen offers a growing collection of immune checkpoint (IC)-related products
(for research use only).
• IC-expressing cell lines
A family of Raji cells to assess the various functionalities of IC targeting monoclonal antibodies (mAbs). They can be used in combination with InvivoGen’s engineered human reporter T-cell lines (Jurkat-Lucia™ NFAT-CD16 cellsand Jurkat-Lucia™ NFAT-CD32 cells) as an alternative to laborious classical antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) assays.
• Anti-IC cell-based assays (BioIC™)
A paired cell line-based assay to screen antibody-, Fc-fusion protein-, or small molecule-based inhibitors of the 4-1BB/4-1BBL, CD27/CD70, ICOS/ICOS-L, and PD-1/PD-L1 axis. Each assay is comprised of a TCR (T cell receptor)-expressing Jurkat reporter cell line and an APC (antigen-presenting cell) Raji cell line. An activating control APC Raji cell line (Raji-APC-Null) is also available.
• Biosimilar IC antibodies in various IgG formats
Families of recombinant clinically-relevant IC targeting mAbs with different IgG isotypes. These can be used to study the effect of the various effector functions (e.g. ADCC) on the efficacy of immune checkpoint therapy [7].
• Mouse anti-mouse IC antibodies for in vivo studies
Recombinant mouse anti-mouse mAbs engineered to limit their immunogenicity for constant efficacy upon repeated injections in mice. Specifically designed for in vivo studies.
Read our review on Immune Checkpoint Blockade
References:
1. Wei, S.C. et al. 2018. Fundamental Mechanisms of Immune Checkpoint Blockade Therapy. Cancer Discov 8, 1069-1086.
2. Paluch, C. et al. 2018. Immune Checkpoints as Therapeutic Targets in Autoimmunity. Front Immunol 9, 2306.
3. Ribas, A. & Wolchok, J.D. 2018. Cancer immunotherapy using checkpoint blockade. Science 359, 1350-1355.
4. Donini, C. et al. 2018. Next-generation immune-checkpoints for cancer therapy. J Thorac Dis 10, S1581-S1601.
5. Mazzarella, L. et al. 2019. The evolving landscape of 'next-generation' immune checkpoint inhibitors: A review. Eur J Cancer 117, 14-31.
6. Chretien, S. et al. 2019. Beyond PD-1/PD-L1 Inhibition: What the Future Holds for Breast Cancer Immunotherapy. Cancers (Basel) 11.
7. Wang, X. et al. 2018. IgG Fc engineering to modulate antibody effector functions. Protein Cell 9, 63-73.