Immun-Checkpoints
A central component of our immune system are T lymphocytes (short: T cells). They belong to the group of leukocytes (white blood cells). In addition to B lymphocytes, they are the most important part of the adaptive immune response. There are receptors on the surface (membrane) of T lymphocytes called immune checkpoints. Because of their influence on the immune response, they are subdividable into anti-inflammatory and proinflammatory immune checkpoints.
The corresponding counterparts to the receptors, the ligands, are located on the surface of other cells. Tumor cells show an overexpression of these proteins, allowing them to escape recognition by T cells. This phenomenon is also called immune evasion.
In medicine, the field of cancer immunotherapy (immune checkpoint therapy) is concerned with immune checkpoint inhibitors. These are substances that bind to immune checkpoints. Thereby, they prevent the possibility of the tumor cell to escape the recognition by T lymphocytes. Consequently, the body's immune response in the fight against the tumor cell is supported by immune checkpoint inhibitors.
Fig.1.: Up. The binding of the over-expressed ligand PD-L1 on the surface of the tumor cell to the immune checkpoint PD-1 inhibits the attack of the T cell.
Down. Blocking this interaction by means of an anti-PD-1 or an anti-PD-L1 antibody prevents the immune evasion of the tumor cell and allows the attack of the T cell on the tumor cell.
The best-known immune checkpoints include PD-1 and CTLA-4. James P. Allison and Tasuku Honjo received the Nobel Prize for Medicine in 2018 for their research on immune checkpoints. The two immuno-checkpoint inhibitors Nivolumab and Ipilimumab were developed against them. This year, our partner Bio X Cell has launched a new anti-VISTA antibody for in vivo use.
Bio X Cell's anti-VISTA represents the revolution in cancer research on immune checkpoints. This monoclonal antibody (13F3) binds to murine V-domain immunoglobulin suppressor of cell activation (VISTA), also known as PD-1H and B7-H5. VISTA is a negative immune checkpoint that inhibits T cell cytokine production and proliferation. Tumor infiltrating lymphocytes (myeloid cells and regulatory T cells) show a marked overexpression of VISTA on their surface. The blocking of VISTA by means of the monoclonal 13F3 antibody has led to delayed tumor growth and represents a promising approach for future cancer immunotherapy.
References regarding the clone 13F3:
Antiinflammatorische Immun-Checkpoints (entzündungsdämpfend)
Target | Manufactuer | Productno. | Amount | References |
A2AR |
Raybiotech
|
STJ91494-50 107-10005 AF-DF4850-100ul
|
50µl 100µl 100µl
|
|
B7-H3 (CD276) |
Bio X Cell |
BE0124-1MG BE0124-5MG BE0124-25MG BE0124-50MG BE0124-100MG
|
1MG 5MG 25MG 50MG 100MG |
Kamachi et al., 2015 Yamato et al., 2009 Nagashima et al., 2008
|
B7-H4 (VTCN1)
|
Raybiotech
|
DS-MB-02774
|
0.1MG
|
Krambeck et al., 2006
|
BTLA
|
Bio X Cell
|
BE0132-1MG BE0132-5MG BE0132-25MG BE0132-50MG BE0132-100MG
|
1MG 5MG 25MG 50MG 100MG |
Bekiaris et al., 2013 Nakagomi et al., 2013 Steinberg et al. 2013
|
CTLA-4
|
Bio X Cell
|
BE0164-1MG BE0164-5MG BE0164-25MG BE0164-50MG BE0164-100MG
|
1MG 5MG 25MG 50MG 100MG |
Dai et al., 2015 Zippelius et al., 2015 Condamine et al. 2014
|
IDO
|
Cosmobio ProSci Boster Boster
|
KAL-KR101 51-473 BOS-M01705 BOS-PA1611
|
150UG 0.05MG 100UL 100UG/vial
|
Fallarino F. et al., 2003 Burkin, D. J. et al., 1993
|
KIR
|
Sino Biological |
13145-R124-50 13145-MM07-50
|
50UG 50UG
|
Fan QR, et al., 2001 |
LAG-3 |
Bio X Cell
|
BE0174-1MG BE0174-5MG BE0174-25MG BE0174-50MG BE0174-100MG
|
1MG 5MG 25MG 50MG 100MG |
Rouhani et al. 2015 Durham et al. 2014 Erickson et al. 2014
|
PD-1 |
Bio X Cell
|
BE0146-1MG BE0146-5MG BE0146-25MG BE0146-50MG BE0146-100MG
|
1MG 5MG 25MG 50MG 100MG |
Moynihan et al. 2016 Evans et al. 2015 Ngiow et al. 2015
|
TIM-3
|
Bio X Cell
|
BE0275-1MG BE0275-5MG BE0275-25MG BE0275-50MG BE0275-100MG
|
1MG 5MG 25MG 50MG 100MG |
Wang et al. 2015 Hongo et al. 2014 Hou et al. 2014
|
VISTA (V-domain Ig suppressor of T cell activation)
|
Bio X Cell
|
BE0310-1MG BE0310-5MG BE310-25MG BE0310-50MG BE0310-100MG
|
1MG 5MG 25MG 50MG 100MG |
Sergent et al. 2018 Srivastava et al. 2018 Ceeraz et al. 2017
|
Proinflammatorische Immun-Checkpoints (entzündungssteigernd)
Target | Manufactuer | Productno. | Amount | References |
CD27 (TNF-Rezeptor-Superfamilie) |
GenScript AVIVA Systems Biology Boster
|
A01964-40 OALA06512 BOS-M01148
|
40µg 50µg 100µg/vial
|
|
CD40 (TNF-Rezeptor-Superfamilie) (weitere Produkte: InVivoPlus anti-mouse CD40)
|
Bio X Cell |
BE0189-1MG BE0189-5MG BE0189-25MG BE0189-50MG BE0189-100MG
|
1MG 5MG 25MG 50MG 100MG |
Bankert, K. C., et al., 2015 Cooley, L. F., et al., 2015 Okimura, K., et al., 2014 Frentsch, M., et al., 2013 Price, A. M., et al., 2012 D'Souza, B. N., et al., 2004 Francisco, J. A., et al., 2000
|
OX40 (TNF-Rezeptor-Superfamilie)
|
Bio X Cell
|
BE0031-1MG BE0031-5MG BE0031-25MG BE0031-50MG BE0031-100MG
|
1MG 5MG 25MG 50MG 100MG |
Bartkowiak, T., et al., 2015 Makkouk, A., et al., 2015 Zander, R. A., et al., 2015 Guo, Z., et al., 2014 Krupnick, A. S., et al., 2014 Redmond, W. L., et al., 2014 Hu, Z., et al., 2013 Kurche, J. S., et al., 2012 Xiao, X., et al., 2012 Murray, S. E., et al., 2011
|
GITR (TNF-Rezeptor-Superfamilie)
|
Bio X Cell
|
BE0063-1MG BE0063-5MG BE0063-25MG BE0063-50MG BE0063-100MG
|
1MG 5MG 25MG 50MG 100MG |
Bartkowiak, T., et al., 2015 Lu, L., et al., 2014 Bulliard, Y., et al., 2013 Cote, A. L., et al., 2011 Johanns, T. M., et al., 2010
|
CD137 (TNF-Rezeptor-Superfamilie)
|
Bio X Cell
|
BE0239-1MG BE0239-5MG BE0239-25MG BE0239-50MG BE0239-100MG
|
1MG 5MG 25MG 50MG 100MG |
Giardino Torchia, M. L., et al., 2015 Guillerey, C., et al., 2015 Tewalt, E. F., et al., 2012 Verbrugge, I., et al., 2012 Vezys, V., et al., 2011
|
CD28 (B7-CD28 Superfamilie)
|
Bio X Cell
|
BE0015-1-1MG BE0015-1-5MG BE0015-1-25MG BE0015-1-50MG BE0015-1-100MG
|
1MG 5MG 25MG 50MG 100MG |
Bertin, S., et al., 2015 Huang, Y., et al., 2015 Klimatcheva, E., et al., 2015 Pallandre, J. R., et al., 2015 Bertin, S., et al., 2014 Heinemann, C., et al., 2014 Vegran, F., et al., 2014 Berger, H., et al., 2013 Chen, E. J., et al., 2013 Nowak, E. C., et al., 2009
|
ICOS (B7-CD28 Superfamilie)
|
Bio X Cell |
BE0059-1MG BE0059-5MG BE0059-25MG BE0059-50MG BE0059-100MG
|
1MG 5MG 25MG 50MG 100MG
|
Liu, D., et al., 2016 Villegas-Mendez, A., et al., 2015 Krupnick, A. S., et al., 2014 Rabant, M., et al., 2013 Charbonnier, L. M., et al., 2012 Kadri, N., et al., 2012
|