Comparison

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)

TargetManufactuerProductno.AmountReferences
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)

TargetManufactuerProductno.AmountReferences
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