Immune Checkpoint Antibodies

 

What are Immune Checkpoints?

 

Immune checkpoints are regulators of the immune system which prevent the immune system from attacking self-antigens indiscriminately.  While this is critical to preventing auto-immune disease it also causes the immune system to be ineffective in eradicating or suppressing cancer.

Tumor cells exploit certain immune-checkpoint pathways as a major mechanism of immune resistance, particularly against T cells that are specific for tumor antigens. Because many of these immune checkpoints are initiated by ligand-receptor interactions, they can be readily blocked by antibodies.

Blocking these immune checkpoints allows antitumor activity to resume and is among the most promising approaches to activating therapeutic anti-tumor immunity.

Bio X Cell offers an extensive selection of antibodies targeting mouse immune checkpoint proteins.

  • 4-1BB is a 39 kDa transmembrane protein expressed by T lymphocytes, NK cells, dendritic cells, granulocytes, and mast cells. Upon binding its ligand 4-1BBL, 4-1BB provides costimulatory signals to both CD4 and CD8 T cells through the activation of NF- κB, c-Jun and p38 downstream pathways. The importance of the 4-1BB pathway has been underscored in a number of diseases, including cancer. Agonistic anti-4-1BB antibodies have been reported to induce T cell-mediated antitumor immunity.

     

    Available anti-mouse 4-1BB antibodies:

    Clone LOB12.3 - This clone was first published in 2002 by Vadim Y. Taraban et al. The immunogen used to create this antibody is reported as a mouse CD137 human Fc fusion protein.

    The original publication describing the generation of this antibody can be found here: https://www.ncbi.nlm.nih.gov/pubmed/12516549

    Further product information and references:

    InVivoMAb anti-mouse 4-1BB (CD137)

    InVivoPlus anti-mouse 4-1BB (CD137)

     

    Clone 3H3 - This clone was first published in 1997 by Walter W. Shuford et al. The immunogen used to create this antibody is reported as a mouse CD137 human Fc fusion protein.

    The original publication describing the generation of this antibody can be found here: https://www.ncbi.nlm.nih.gov/pubmed/9206996

    Further product information and references:

    InVivoMAb anti-mouse 4-1BB (CD137)

     

    Clone 17B5 - Origin information unknown

    Further product information and references:

    InVivoMAb anti-mouse 4-1BB (CD137)

  • 4-1BBL is a 97 kDa member of the TNF superfamily and is expressed by dendritic cells, macrophages, and activated B and T lymphocytes. Interaction of 4-1BBL with 4-1BB (CD137) provides costimulatory signals to both CD4 and CD8 T cells through the activation of NF-κB, c-Jun, and p38 downstream pathways.

     

    Available anti-mouse 4-1BBL antibodies:

    Clone TKS-1 - This clone was first published in 2002 by Toshiro Futagawa et al. The immunogen used to create this antibody is reported as mouse 4-1BBL transfected NRK cells.

    The original publication describing the generation of this antibody can be found here: https://www.ncbi.nlm.nih.gov/pubmed/11867564

    Further product information and references:

    InVivoMAb anti-mouse 4-1BBL (CD137L)

  • CD40 is expressed broadly on antigen-presenting cells (APCs) such as dendritic cells, B cells, macrophages, and monocytes as well as non-immune endothelial cells, basal epithelial cells, and a range of tumors. Upon binding to its ligand CD154, CD40 acts as a costimulatory molecule for the activation of B cells, dendritic cells, monocytes, and other APCs. CD40 plays roles in B cell activation, differentiation, proliferation and Ig isotype switching as well as dendritic cell maturation. Agonistic CD40 monoclonal antibodies have been shown to activate APCs and promote anti-tumor T cell responses.

     

    Available anti-mouse CD40 antibodies:

    Clone FGK4.5 - This clone was created in 1996 by Drs. J. Andersson and A. Rolink. The immunogen used to create this antibody is reported as recombinant mouse CD40 fusion protein.

    The original publication describing the generation of this antibody can be found here: https://www.ncbi.nlm.nih.gov/pubmed/8885865

    Further product information and references:

    InVivoMAb anti-mouse CD40

    InVivoPlus anti-mouse CD40

  • CD154 is primarily expressed on the surface of activated CD4+ T lymphocytes but can also be expressed by platelets, mast cells, macrophages, basophils, NK cells, B lymphocytes, CD8+ T lymphocytes as well as non-hematopoietic cells including smooth muscle cells, endothelial cells, and epithelial cells. CD154 signals through CD40 and is thought to play a key role in T and B lymphocyte costimulation. Anti-CD154 antibodies have been reported to inhibit the formation of germinal centers and disrupt antigen-specific T cell responses.

     

    Available anti-mouse CD40L antibodies:

    Clone MR-1 - This clone was first published in 1992 by Dr. Randolph. J. Noelle et al. The immunogen used to create this antibody is reported as activated mouse TH1 clone D1.6.

    The original publication describing the generation of this antibody can be found here: https://www.ncbi.nlm.nih.gov/pubmed/1378631

    Further product information and references:

    InVivoMAb anti-mouse CD40L (CD154)

    InVivoPlus anti-mouse CD40L (CD154)

  • CD47 is ubiquitously expressed by both hematopoietic cells such as T and B lymphocytes, monocytes, platelets and erythrocytes and non-hematopoietic cells. CD47 is involved in a range of cellular processes, including apoptosis, proliferation, adhesion, and migration. Furthermore, it plays a key role in immune and angiogenic responses. CD47 is a receptor for thrombospondin-1 (TSP-1), a secreted glycoprotein that plays a role in vascular development and angiogenesis. CD47 Is has been found to be overexpressed in many different tumor cells. Because of this, anti-CD47 monoclonal antibodies have been proposed and studied as a therapeutic treatment for human cancers.

     

    Available anti-mouse CD47 antibodies:

    Clone MIAP301 – Origin information unknown

    Further product information and references:

    InVivoMAb anti-mouse CD47 (IAP)

     

    Clone MIAP410 - This clone was first published in 2000 by Xin Han et al. The immunogen used to create this antibody is reported as purified human placental CD47.

    The original publication describing the generation of this antibody can be found here: https://www.ncbi.nlm.nih.gov/pubmed/10964914

    Further product information and references:

    InVivoMAb anti-mouse/human/rat CD47 (IAP)

  • CD80 is expressed by activated B cells and constitutively by monocytes and dendritic cells. This ligand binds to CD28 to provide a costimulatory signal necessary for T cell activation and survival, and cytokine production. Additionally, CD80 binds to CTLA-4 which inhibits T cells.

     

    Available anti-mouse CD80 antibodies:

    Clone 1G10 - This clone was first published in 1992 by Ziba Razi-Wolf et al. The immunogen used to create this antibody is reported as dibutyryl cAMP-Activated 5C2 cells.

    The original publication describing the generation of this antibody can be found here: https://www.ncbi.nlm.nih.gov/pubmed/1373896

    Further product information and references:

    InVivoMAb anti-mouse CD80 (B7-1)

     

    Clone 16-10A1 - This clone was first published in 1994 by Gordon D.Powers et al. The immunogen used to create this antibody is reported as CHO cells transfected with mouse CD80.

    The original publication describing the generation of this antibody can be found here: https://www.ncbi.nlm.nih.gov/pubmed/7509723

    Further product information and references:

    InVivoMAb anti-mouse CD80 (B7-1)

  • CD86 is expressed by activated T and B cells, macrophages, and dendritic cells. This ligand binds to CD28 to provide a costimulatory signal necessary for T cell activation and survival, and cytokine production. Additionally, CD80 binds to CTLA-4 which inhibits T cells.

     

    Available anti-mouse CD86 antibodies:

    Clone GL-1 - This clone was first published in 1993 by Karen S. Hathcock et al. The immunogen used to create this antibody is reported as LPS-activated CBA/Ca mouse splenic B cells.

    The original publication describing the generation of this antibody can be found here: https://www.ncbi.nlm.nih.gov/pubmed/7694361

    Further product information and references:

    InVivoMAb anti-mouse CD86 (B7-2)

  • CD276 is expressed weakly on activated lymphocytes, macrophages, dendritic cells, nasal and airway epithelial cells, osteoblasts, and some tumor cell lines. A soluble form of CD276 is also secreted by monocytes, dendritic cells, and activated T cells. The biological role of CD276 is still under investigation however, recent studies suggest a negative regulatory role for CD276 in T cell responses.

     

    Available anti-mouse CD276 antibodies:

    Clone MJ18 - This clone was first published in 2008 by Osamu Nagashima et al. The immunogen used to create this antibody is reported as a mouse B7-H3 IgG2a fusion protein.

    The original publication describing the generation of this antibody can be found here: https://www.ncbi.nlm.nih.gov/pubmed/18768862

    Further product information and references:

    InVivoMAb anti-mouse CD276 (B7-H3)

  • CTLA-4 is expressed on activated T and B lymphocytes. CTLA-4 is structurally similar to the T-cell co-stimulatory protein, CD28, and both molecules bind to the B7 family members B7-1 (CD80) and B7-2 (CD86). Upon ligand binding, CTLA-4 negatively regulates cell-mediated immune responses. CTLA-4 plays roles in induction and/or maintenance of immunological tolerance, thymocyte development, and regulation of protective immunity. The critical role of CTLA-4 in immune down-regulation has been demonstrated in CTLA-4 deficient mice, which succumb at 3-5 weeks of age due to the development of a lymphoproliferative disease. CTLA-4 is among a group of inhibitory receptors being explored as cancer treatment targets through immune checkpoint blockade.

     

    Available anti-mouse CTLA-4 antibodies:

    Clone 9H10 - This clone was first published in 1995 by Matthew F. Krummel and James P. Allison. The immunogen used to create this antibody is reported as mouse CTLA-4-human IgG1 fusion protein.

    The original publication describing the generation of this antibody can be found here: https://www.ncbi.nlm.nih.gov/pubmed/7543139

    Further product information and references:

    InVivoMAb anti-mouse CTLA-4 (CD152)

    InVivoPlus anti-mouse CTLA-4 (CD152)

     

    Clone 9D9 - Origin information unknown

    Further product information and references:

    InVivoMAb anti-mouse CTLA-4 (CD152)

    InVivoPlus anti-mouse CTLA-4 (CD152)

     

    Clone UC10-4F10-11 - This clone was first published in 1994 by Theresa L. Walunas. The immunogen used to create this antibody is reported as mouse CTLA-4 IgG2a fusion protein.

    The original publication describing the generation of this antibody can be found here: https://www.ncbi.nlm.nih.gov/pubmed/7882171

    Further product information and references:

    InVivoMAb anti-mouse CTLA-4 (CD152)

    InVivoPlus anti-mouse CTLA-4 (CD152)

  • LAG-3 is expressed by activated T lymphocytes, NK cells, and T regulatory cells. LAG-3’s main ligand is MHC class II which it binds to with a higher affinity than even CD4 does. Upon binding LAG-3 is thought to play similar roles as CTLA-4 and PD-1 including downregulation of TCR signaling and inhibition of CD4-dependent T cell function. LAG-3 has also been demonstrated to contribute to the suppressor function of T regulatory cells. In contrast to inhibition, LAG-3 has been shown to promotes immune responses by activating antigen-presenting cells.

     

    Available anti-mouse LAG-3 antibodies:

    Clone C9B7W - This clone was first published in 2002 by Creg J. Workman et al. The immunogen used to create this antibody is reported as a mouse CD223-Ig fusion protein.

    The original publication describing the generation of this antibody can be found here: https://www.ncbi.nlm.nih.gov/pubmed/12209638

    Further product information and references:

    InVivoMAb anti-mouse LAG-3

    InVivoPlus anti-mouse LAG-3

  • OX-40 is expressed on activated CD4 and CD8 T cells but is not found on resting naïve T cells or most resting memory T cells. Although it was originally thought that OX-40 expression was restricted to activated conventional T cells, it has now been visualized on activated regulatory T cells, NKT cells, NK cells, and neutrophils. OX-40 plays a major role in regulating both CD4 and CD8 T cell clonal expansion. It provides a costimulatory signal to antigen-reacting naive T cells to prolong proliferation, as well as augment the production of several cytokines. This is demonstrated by OX-40 knockout mice which generate fewer primary effector CD4 T cells after immunization. Furthermore, in vivo treatment with an agonist antibody to OX-40 has been shown to strongly enhance the generation of antigen-specific effector T cells and prevent the induction of T cell tolerance.

     

    Available anti-mouse OX40 antibodies:

    Clone OX-86 - This clone was first published in 1996 by Aymen Al-Shamkhani et al. The immunogen used to create this antibody is reported as recombinant mouse OX40-CD4 chimeric protein.

    The original publication describing the generation of this antibody can be found here: https://www.ncbi.nlm.nih.gov/pubmed/8765008

    Further product information and references:

    InVivoMAb anti-mouse OX40 (CD134)

    InVivoPlus anti-mouse OX40 (CD134)

  • OX40L is expressed on activated B cells and antigen presenting cells. OX40L is the ligand for OX40 (CD134). OX40 signaling regulates both CD4 and CD8 T cell clonal expansion. It provides a costimulatory signal to antigen-reacting naive T cells to prolong proliferation, as well as augment the production of several cytokines including IL-2.

     

    Available anti-mouse OX40L antibodies:

    Clone RM134L - This clone was first published in 1999 by Yoshinori Seko et al. The immunogen used to create this antibody is reported as rat NRK-52E cells transfected with mouse OX40L.

    The original publication describing the generation of this antibody can be found here: https://www.ncbi.nlm.nih.gov/pubmed/10440754

    Further product information and references:

    InVivoMAb anti-mouse OX40L (CD134L)

  • PD-1 is transiently expressed on CD4 and CD8 thymocytes as well as activated T and B lymphocytes and myeloid cells. PD-1 expression declines after successful elimination of antigen. Additionally, Pdcd1 mRNA is expressed in developing B lymphocytes during the pro-B-cell stage. PD-1’s structure includes an ITIM (immunoreceptor tyrosine-based inhibitory motif) suggesting that PD-1 negatively regulates TCR signals. PD-1 signals via binding its two ligands, PD-L1 and PD-L2 both members of the B7 family. Upon ligand binding, PD-1 signaling inhibits T-cell activation, leading to reduced proliferation, cytokine production, and T-cell death. Additionally, PD-1 is known to play key roles in peripheral tolerance and prevention of autoimmune disease in mice as PD-1 knockout animals show dilated cardiomyopathy, splenomegaly, and loss of peripheral tolerance. Induced PD-L1 expression is common in many tumors including squamous cell carcinoma, colon adenocarcinoma, and breast adenocarcinoma. PD-L1 overexpression results in increased resistance of tumor cells to CD8 T cell-mediated lysis. In mouse models of melanoma, tumor growth can be transiently arrested via treatment with antibodies which block the interaction between PD-L1 and its receptor PD-1. For these reasons anti-PD-1 mediated immunotherapies are currently being explored as cancer treatments.

     

    Available anti-mouse PD-1 antibodies:

    Clone RMP1-14 - This clone was first published in 2003 by Takanori Kanai et al. The immunogen used to create this antibody is reported as Syrian hamster BKH cells transfected with mouse PD-1 cDNA.

    The original publication describing the generation of this antibody can be found here: https://www.ncbi.nlm.nih.gov/pubmed/14530338

    Further product information and references:

    InVivoMAb anti-mouse PD-1 (CD279)

    InVivoPlus anti-mouse PD-1 (CD279)

     

    Clone 29F.1A12 - This clone was first published in 2003 by Spencer C. Liang et al. The immunogen used to create this antibody is reported as a recombinant mouse PD-1-Ig fusion protein.

    The original publication describing the generation of this antibody can be found here: https://www.ncbi.nlm.nih.gov/pubmed/14515254

    Further product information and references:

    InVivoMAb anti-mouse PD-1 (CD279)

    InVivoPlus anti-mouse PD-1 (CD279)

     

    Clone J43 - This clone was first published in 1996 by Yasutoshi Agata et al. The immunogen used to create this antibody is reported as Syrian hamster BKH cells transfected with mouse PD-1 cDNA.

    The original publication describing the generation of this antibody can be found here: https://www.ncbi.nlm.nih.gov/pubmed/8671665

    Further product information and references:

    InVivoMAb anti-mouse PD-1 (CD279)

    InVivoPlus anti-mouse PD-1 (CD279)

  • PD-L1 is expressed on T lymphocytes, B lymphocytes, NK cells, dendritic cells, as well as IFNγ stimulated monocytes, epithelial cells, and endothelial cells. PD-L1 binds to its receptor, PD-1, found on CD4 and CD8 thymocytes as well as activated T and B lymphocytes and myeloid cells. Engagement of PD-L1 with PD-1 leads to inhibition of TCR-mediated T cell proliferation and cytokine production. PD-L1 is thought to play an important role in tumor immune evasion. Induced PD-L1 expression is common in many tumors and results in increased resistance of tumor cells to CD8 T cell-mediated lysis. In mouse models of melanoma, tumor growth can be transiently arrested via treatment with antibodies which block the interaction between PD-L1 and PD-1.

     

    Available anti-mouse PD-L1 antibodies:

    Clone 10F.9G2 - This clone was first published in 2002 by Michael J. Eppihimer et al. The immunogen used to create this antibody is reported as CHO-mPD-L1 transfectants.

    The original publication describing the generation of this antibody can be found here: https://www.ncbi.nlm.nih.gov/pubmed/11932780

    Further product information and references:

    InVivoMAb anti-mouse PD-L1 (B7-H1)

    InVivoPlus anti-mouse PD-L1 (B7-H1)

  • PD-L2 is a 25 kDa type I transmembrane protein that belongs to the B7 family of the Ig superfamily. PD-L2 is expressed on monocytes, macrophages, and subsets of dendritic cells. PD-L2 binds to its receptor, PD-1, found on CD4 and CD8 thymocytes as well as activated T and B lymphocytes and myeloid cells. Engagement of PD-L2 with PD-1 leads to inhibition of TCR-mediated T cell proliferation and cytokine production.

     

    Available anti-mouse PD-L2 antibodies:

    Clone TY25 - This clone was first published in 2002 by Tomohide Yamazaki et al. The immunogen used to create this antibody is reported as mouse B7-DC-transfected RAW264.7 cells.

    The original publication describing the generation of this antibody can be found here: https://www.ncbi.nlm.nih.gov/pubmed/12421930

    Further product information and references:

    InVivoMAb anti-mouse PD-L2 (B7-DC)

  • TIM-1 is a type I cell-surface glycoprotein and member of the Ig superfamily. TIM-1 is preferentially expressed on TH2 cells and has been identified as a stimulatory molecule for T cell activation. The TIM gene family plays critical roles in regulating the immune response to viral infection. TIM-1 is also involved in allergic responses, asthma, and transplant tolerance.

     

    Available anti-mouse TIM-1 antibodies:

    Clone RMT1-10 - This clone was first published in 2006 by Atsuki Fukushima et al. The immunogen used to create this antibody is reported as a full-length mouse TIM-1-Ig fusion protein.

    The original publication describing the generation of this antibody can be found here: https://www.ncbi.nlm.nih.gov/pubmed/17174273

    Further product information and references:

    InVivoMAb anti-mouse TIM-1 (CD365)

     

    Clone 3B3 - This clone was first published in 2005 by Sarah E Umetsu et al. The immunogen used to create this antibody is reported as a mouse TIM-1 (signal and IgV domains)/mouse IgG2a Fc fusion protein.

    The original publication describing the generation of this antibody can be found here: https://www.ncbi.nlm.nih.gov/pubmed/15793575

    Further product information and references:

    InVivoMAb anti-mouse TIM-1 (CD365)

  • TIM-3 is specifically expressed at high levels on the surface of Th1 lymphocytes whereas Th2 lymphocytes express TIM-1 and TIM-2. TIM-3 activation occurs via binding to the cell-associated C-type lectin galectin-9. Upon binding TIM-3 induces apoptosis of Th1 cells. Inhibition of TIM-3 signaling in mice has been shown to exacerbate experimental autoimmune encephalomyelitis, promote IFNγ production and Th1 cell proliferation. Tim-3 has also been shown to be required for the induction of tolerance, as both TIM-3 knockout animals and mice treated with TIM-3-Ig fusion protein display defects in the induction of antigen-specific tolerance. Additionally, TIM-3 signaling is currently being explored as a cancer immunotherapy target as CD8 T cells which express both TIM-3 and PD-1 exhibit greater defects in both cell-cycle progression and effector cytokine production than cells that express PD-1 alone.

     

    Available anti-mouse TIM-3 antibodies:

    Clone RMT3-23 - This clone was first published in 2006 by Tsunekazu Oikawa et al. The immunogen used to create this antibody is reported as recombinant mouse TIM-3.

    The original publication describing the generation of this antibody can be found here: https://www.ncbi.nlm.nih.gov/pubmed/16982862

    Further product information and references:

    InVivoMAb anti-mouse TIM-3 (CD366)

    InVivoPlus anti-mouse TIM-3 (CD366)

     

    Clone B8.2C12 - Origin information unknown

    Further product information and references:

    InVivoMAb anti-mouse TIM-3 (CD366)