Cancer Immune Checkpoints

Immune checkpoints are receptors on the membrane of T-lymphocytes that can regulate their immune response. They are refinely tuned and alternate between stimulation and inhibition1. The immuno checkpoints pathway is crucial to promote self-tolerance and prevent autoimmunity and related diseases.

T-cell receptors are in focus of medical research, however, global immunosuppression greatly increases the risk of acquiring life-threatening infections and is associated with organ toxicity when used long-term. Thus, alternative approaches that inhibit only the unwanted immune responses and preserve general immunity are highly desirable.

Antibodies and ELISA Kits for Cancer Immune Checkpoints

The tumor necrosis factor (TNF) receptor superfamily represents largest part of receptors with CD27, CD40, OX40, GITR and CD137. Another two stimulatory checkpoint molecules belongs to the B7-CD28 superfamily; CD28 itself and ICOS.1

Co-Stimulation and Inhibition with BTLA and HVEM

The HVEM/ LIGHT/BTLA/CD160 costimulatory/coinhibitory pathway has emerged as a potential target for the development of immune therapeutic interventions. The interaction between BTLA, short for B and T Lymphocyte Attenuator, an inhibitory receptor whose extracellular domain belongs to the immunoglobulin superfamily, and herpesvirus-entry mediator (HVEM), a co-stimulatory tumour-necrosis factor receptor, is unique in that it is the only receptor–ligand interaction that directly links these two families of receptors.2

Recent studies show that engagement of HVEM with its endogenous ligand (LIGHT) from the tumour-necrosis factor family induces a powerful immune response. LIGHT stimulates the proliferation of T cells, and triggers apoptosis of various tumor cells, whereas HVEM interactions with BTLA negatively regulate T-cell responses.3

Checkpoint Inhibitors Important for Cancer Immunotherapy

Inhibitory checkpoint molecules are promising targets for cancer immunotherapy. The discovery and clinical application of immune-checkpoint inhibitors has dramatically improved the treatments, outcomes and therapeutic concepts in multiple tumor settings.

Of the immune checkpoint proteins identified to date, CTLA-4 is a critical regulator of T-cell responses4. CTLA-4 is structurally similar to the co-stimulating receptor CD28, with both receptors also binding to CD80 and CD86 (also known as B7-1 and B7-2). Binding to CD80 or CD86 leads to a competition between an inhibitory signal (by CTLA-4) and a co-stimulating signal (by CD28).

In 2018 the research on monoclonal antibodies blocking the inhibitory molecule CTLA-4 and or the PD-1/PD-L1 axis by James P. Allison & Tasuku Honjo, was awarded with The Nobel Prize in Physiology or Medicine.5


References:

  1. Kyung H. Yi (2009): "Fine tuning the immune response through B7-H3 and B7-H4”. Immunol Rev2009 May; 229(1): 145–151. [PMID: 2696224]
  2. Kenneth M. Murphy, Christopher A Nelson, John R. Sedy (2006): "Balancing co-stimulation and inhibition with BTLA and HVEM”. Nature Reviews Immunology6, 671-681[PMID: 2811435]
  3. Maria Luisa del Rio et Al (2016): “Immunotherapeutic targeting of LIGHT/LTβR/HVEM pathway fully recapitulates the reduced cytotoxic phenotype of LIGHT-deficient T cells” MAbs, Apr; 8(3): 478–490. [PMID: 4966841]
  4. Behzad Rowshanravan, Neil Halliday and David M. Sansom (2018): “CTLA-4: a moving target in immunotherapy”. Blood, 1131:58-67; [PMID: 741033]
  5. James P. Allison and Tasuku Honjo (2018): “for their discovery of cancer therapy by inhibition of negative immune regulation”. The Nobel Assembly at Karolinska Institutet [Press Release]

Major Histocompatibility Complex

HLA-A (Major Histocompatibility Complex, Class I, A):

HLA-A belongs to the HLA class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. Class I molecules play a central role in the immune system by presenting peptides derived from the endoplasmic reticulum lumen. They are expressed in nearly all cells. The heavy chain is...   More...

MR1 (Major Histocompatibility Complex, Class I-Related):

CIITA - Class II, Major Histocompatibility Complex, Transactivator

Antigens in this category:
HLA-B (Major Histocompatibility Complex, Class I, B): HLA-B antibodies HLA-B ELISA Kits HLA-B Proteins
HLA-ABC - HLA-ABC: HLA-ABC antibodies    
HLA-DMA - Major Histocompatibility Complex, Class II, DM alpha: HLA-DMA antibodies HLA-DMA ELISA Kits HLA-DMA Proteins
HLA-DMB (Major Histocompatibility Complex, Class II, DM beta): HLA-DMB antibodies   HLA-DMB Proteins
HLA-DOB (Major Histocompatibility Complex, Class II, DO beta): HLA-DOB antibodies   HLA-DOB Proteins
HLA-DPA1 - Major Histocompatibility Complex, Class II, DP alpha 1: HLA-DPA1 antibodies   HLA-DPA1 Proteins
HLA-DPB1 (Major Histocompatibility Complex, Class II, DP beta 1): HLA-DPB1 antibodies   HLA-DPB1 Proteins
HLA-DQA1 - Major Histocompatibility Complex, Class II, DQ alpha 1: HLA-DQA1 antibodies   HLA-DQA1 Proteins
HLA-DQB1 (Major Histocompatibility Complex, Class II, DQ beta 1): HLA-DQB1 antibodies HLA-DQB1 ELISA Kits HLA-DQB1 Proteins
HLA-DRB1 (Major Histocompatibility Complex, Class II, DR beta 1): HLA-DRB1 antibodies HLA-DRB1 ELISA Kits HLA-DRB1 Proteins
HLA-DRB3 (Major Histocompatibility Complex, Class II, DR beta 3): HLA-DRB3 antibodies   HLA-DRB3 Proteins
HLA-DRB5 (Major Histocompatibility Complex, Class II, DR beta 5): HLA-DRB5 antibodies HLA-DRB5 ELISA Kits HLA-DRB5 Proteins
PTCRA (Pre T-Cell Antigen Receptor alpha): PTCRA antibodies   PTCRA Proteins
CD74 (HLA-DR-gamma): CD74 antibodies CD74 ELISA Kits CD74 Proteins

Stimulatory T-Cell Receptors

CTLA4 (Cytotoxic T-Lymphocyte-Associated Protein 4):

This gene is a member of the immunoglobulin superfamily and encodes a protein which transmits an inhibitory signal to T cells. The protein contains a V domain, a transmembrane domain, and a cytoplasmic tail. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. The membrane-bound isoform functions as a homodimer interconnected by a disulfide bond,...   More...

CD274 - PD-L1

TNFSF4 (Tumor Necrosis Factor (Ligand) Superfamily, Member 4):

Antigens in this category:
ADORA2A - Adenosine A2a Receptor: ADORA2A antibodies ADORA2A ELISA Kits ADORA2A Proteins
ACVR2B - Activin A Receptor, Type IIB: ACVR2B antibodies ACVR2B ELISA Kits ACVR2B Proteins
CD226 (CD226 Molecule): CD226 antibodies CD226 ELISA Kits CD226 Proteins
CD27 (CD27 Molecule): CD27 antibodies CD27 ELISA Kits CD27 Proteins
CD276 (CD276 Molecule): CD276 antibodies CD276 ELISA Kits CD276 Proteins
CD40LG - CD40 Ligand: CD40LG antibodies CD40LG ELISA Kits CD40LG Proteins
CD40 (CD40 Molecule, TNF Receptor Superfamily Member 5): CD40 antibodies CD40 ELISA Kits CD40 Proteins
CD70 (CD70 Molecule): CD70 antibodies CD70 ELISA Kits CD70 Proteins
CD80 (CD80): CD80 antibodies CD80 ELISA Kits CD80 Proteins
ICOS (Inducible T-Cell Co-Stimulator): ICOS antibodies ICOS ELISA Kits ICOS Proteins
PVR - Poliovirus Receptor: PVR antibodies PVR ELISA Kits PVR Proteins
PDCD1 - PD-1: PDCD1 antibodies PDCD1 ELISA Kits PDCD1 Proteins
TNFSF9 (Tumor Necrosis Factor (Ligand) Superfamily, Member 9): TNFSF9 antibodies TNFSF9 ELISA Kits TNFSF9 Proteins
TNFRSF18 (Tumor Necrosis Factor Receptor Superfamily, Member 18): TNFRSF18 antibodies TNFRSF18 ELISA Kits TNFRSF18 Proteins
TNFRSF4 - Tumor Necrosis Factor Receptor Superfamily, Member 4: TNFRSF4 antibodies TNFRSF4 ELISA Kits TNFRSF4 Proteins
TNFRSF9 - CD137: TNFRSF9 antibodies TNFRSF9 ELISA Kits TNFRSF9 Proteins

Inhibitory T-Cell Receptors

BTLA (B and T Lymphocyte Associated):

Antigens in this category:
KIR2DL3 (Killer Cell Immunoglobulin-Like Receptor, Two Domains, Long Cytoplasmic Tail, 3): KIR2DL3 antibodies KIR2DL3 ELISA Kits KIR2DL3 Proteins
TIGIT (T Cell Immunoreceptor with Ig and ITIM Domains): TIGIT antibodies TIGIT ELISA Kits TIGIT Proteins
TIMD4 (T-Cell Immunoglobulin and Mucin Domain Containing 4): TIMD4 antibodies TIMD4 ELISA Kits TIMD4 Proteins
TNFSF14 (Tumor Necrosis Factor (Ligand) Superfamily, Member 14): TNFSF14 antibodies TNFSF14 ELISA Kits TNFSF14 Proteins
TNFRSF14 (Tumor Necrosis Factor Receptor Superfamily, Member 14): TNFRSF14 antibodies TNFRSF14 ELISA Kits TNFRSF14 Proteins

Cytokines

IL1A (Interleukin 1 alpha):

IL1B (Interleukin 1, beta):

Antigens in this category:
IL1F6 - Interleukin 1 Family, Member 6: IL1F6 antibodies IL1F6 ELISA Kits IL1F6 Proteins
IL1RN (Interleukin 1 Receptor Antagonist): IL1RN antibodies IL1RN ELISA Kits IL1RN Proteins
IL10 - IL-10: IL10 antibodies IL10 ELISA Kits IL10 Proteins
IL12 (Interleukin 12): IL12 antibodies IL12 ELISA Kits IL12 Proteins
IL18 - IL 18: IL18 antibodies IL18 ELISA Kits IL18 Proteins
IL6 - Interleukin 6: IL6 antibodies IL6 ELISA Kits IL6 Proteins
IL6RA (Interleukin 6 Receptor, alpha): IL6RA antibodies IL6RA ELISA Kits IL6RA Proteins
IL6ST (Interleukin 6 Signal Transducer (Gp130, Oncostatin M Receptor)): IL6ST antibodies IL6ST ELISA Kits IL6ST Proteins
IL6R - IL-6 Receptor: IL6R antibodies IL6R ELISA Kits IL6R Proteins
TGFB1 (Transforming Growth Factor, beta 1): TGFB1 antibodies TGFB1 ELISA Kits TGFB1 Proteins
IL1R1 (Interleukin 1 Receptor, Type I): IL1R1 antibodies IL1R1 ELISA Kits IL1R1 Proteins