Cluster of differentiation refers to an attempt to catalogue systematically a series of over 300 cell-surface proteins associated with immunotyping. Many members of the group have identified functions as enzymes (for example, see CD73 ecto-5'-nucleotidase) or receptors (for example, see CD41 integrin, alpha 2b subunit). Many CDs are targeted for therapeutic gain using antibodies for the treatment of proliferative disorders. A full listing of all the Clusters of Differentiation proteins is not possible in the Guide to PHARMACOLOGY; listed herein are selected members of the family targeted for therapeutic gain.

The endogenous ligands for human PD-1 are programmed cell death 1 ligand 1 (PD-L1 aka CD274 (CD274, Q9NZQ7)) and programmed cell death 1 ligand 2 (PD-L2; PDCD1LG2). These ligands are cell surface peptides, normally involved in immune system regulation. Expression of PD-1 by cancer cells induces immune tolerance and evasion of immune system attack. Anti-PD-1 monoclonal antibodies are used to induce immune checkpoint blockade as a therapeutic intervention in cancer, effectively re-establishing immune vigilance. Pembrolizumab was the first anti-PD-1 antibody to be approved by the US FDA.

* Key recommended reading is highlighted with an asterisk

* Gabius HJ, Kaltner H, Kopitz J, André S. (2015) The glycobiology of the CD system: a dictionary for translating marker designations into glycan/lectin structure and function. Trends Biochem. Sci., 40 (7): 360-76. [PMID:25981696]

* Vosoughi T, Bagheri M, Hosseinzadeh M, Ehsanpour A, Davari N, Saki N. (2019) CD markers variations in chronic lymphocytic leukemia: New insights into prognosis. J. Cell. Physiol., 234 (11): 19420-19439. [PMID:31049958]

1. Alduaij W, Ivanov A, Honeychurch J, Cheadle EJ, Potluri S, Lim SH, Shimada K, Chan CH, Tutt A, Beers SA et al.. (2011) Novel type II anti-CD20 monoclonal antibody (GA101) evokes homotypic adhesion and actin-dependent, lysosome-mediated cell death in B-cell malignancies. Blood, 117 (17): 4519-29. [PMID:21378274]

2. Bernstein ID. (2000) Monoclonal antibodies to the myeloid stem cells: therapeutic implications of CMA-676, a humanized anti-CD33 antibody calicheamicin conjugate. Leukemia, 14 (3): 474-5. [PMID:10720144]

3. Bolt S, Routledge E, Lloyd I, Chatenoud L, Pope H, Gorman SD, Clark M, Waldmann H. (1993) The generation of a humanized, non-mitogenic CD3 monoclonal antibody which retains in vitro immunosuppressive properties. Eur. J. Immunol., 23 (2): 403-11. [PMID:8436176]

4. Burton JD, Ely S, Reddy PK, Stein R, Gold DV, Cardillo TM, Goldenberg DM. (2004) CD74 is expressed by multiple myeloma and is a promising target for therapy. Clin. Cancer Res., 10 (19): 6606-11. [PMID:15475450]

5. Caron PC, Co MS, Bull MK, Avdalovic NM, Queen C, Scheinberg DA. (1992) Biological and immunological features of humanized M195 (anti-CD33) monoclonal antibodies. Cancer Res., 52 (24): 6761-7. [PMID:1458463]

6. Carven GJ, Van Eenennaam H, Dulos GJ. (2010) Antibodies to human programmed death receptor PD-1. Patent number: US20100266617. Assignee: Organon NV. Priority date: 13/06/2008. Publication date: 21/10/2010.

7. Charrin S, le Naour F, Silvie O, Milhiet PE, Boucheix C, Rubinstein E. (2009) Lateral organization of membrane proteins: tetraspanins spin their web. Biochem. J., 420 (2): 133-54. [PMID:19426143]

8. da Silva AJ, Brickelmaier M, Majeau GR, Li Z, Su L, Hsu YM, Hochman PS. (2002) Alefacept, an immunomodulatory recombinant LFA-3/IgG1 fusion protein, induces CD16 signaling and CD2/CD16-dependent apoptosis of CD2(+) cells. J. Immunol., 168 (9): 4462-71. [PMID:11970990]

9. De Weers M, Graus Y, Oprins J, Parren P, Van De Winkel J, Van Vugt M. (2010) Antibodies Against Cd38 For Treatment Of Multiple Myeloma. Patent number: US7829673. Assignee: Genmab A/S. Priority date: 23/03/2005. Publication date: 09/11/2010.

10. Giger RJ, Hollis 2nd ER, Tuszynski MH. (2010) Guidance molecules in axon regeneration. Cold Spring Harb Perspect Biol, 2 (7): a001867. [PMID:20519341]

11. Ginaldi L, De Martinis M, Matutes E, Farahat N, Morilla R, Dyer MJ, Catovsky D. (1998) Levels of expression of CD52 in normal and leukemic B and T cells: correlation with in vivo therapeutic responses to Campath-1H. Leuk. Res., 22 (2): 185-91. [PMID:9593475]

12. Goldstein G. (1987) Overview of the development of Orthoclone OKT3: monoclonal antibody for therapeutic use in transplantation. Transplant. Proc., 19 (2 Suppl 1): 1-6. [PMID:3105134]

13. Halk EL, Korman AJ, Lonberg N. (2001) Human ctla-4 antibodies and their uses. Patent number: WO2001014424. Assignee: Medarex Inc. Priority date: 24/08/1999. Publication date: 01/03/2001.

14. Hall KT, Boumsell L, Schultze JL, Boussiotis VA, Dorfman DM, Cardoso AA, Bensussan A, Nadler LM, Freeman GJ. (1996) Human CD100, a novel leukocyte semaphorin that promotes B-cell aggregation and differentiation. Proc. Natl. Acad. Sci. U.S.A., 93 (21): 11780-5. [PMID:8876214]

15. Hall RD, Gray JE, Chiappori AA. (2013) Beyond the standard of care: a review of novel immunotherapy trials for the treatment of lung cancer. Cancer Control, 20 (1): 22-31. [PMID:23302904]

16. Hanson DC, Neveu MJ, Mueller EE, Hanke JH, Gilman SC, Davis CG, Corvalan JR. (2004) Human monoclonal antibodies to CTLA-4. Patent number: US6682736 B1. Assignee: Abgenix, Inc., Pfizer Inc.. Priority date: 22/12/1998. Publication date: 27/01/2004.

17. Kline J, Gajewski TF. (2010) Clinical development of mAbs to block the PD1 pathway as an immunotherapy for cancer. Curr Opin Investig Drugs, 11 (12): 1354-9. [PMID:21154117]

18. Korman AJ, Srinivasan M, Wang C, Selby MJ, Chen B, Cardarelli JM. (2006) Human monoclonal antibodies to programmed death 1(pd-1) and methods for treating cancer using anti-pd-1 antibodies alone or in combination with other immunotherapeutics. Patent number: WO2006121168. Assignee: Ono Pharmaceutical Co. Priority date: 09/05/2005. Publication date: 02/03/2015.

19. Latek R, Fleener C, Lamian V, Kulbokas 3rd E, Davis PM, Suchard SJ, Curran M, Vincenti F, Townsend R. (2009) Assessment of belatacept-mediated costimulation blockade through evaluation of CD80/86-receptor saturation. Transplantation, 87 (6): 926-33. [PMID:19300198]

20. Levy S, Shoham T. (2005) The tetraspanin web modulates immune-signalling complexes. Nat. Rev. Immunol., 5 (2): 136-48. [PMID:15688041]

21. Linke R, Klein A, Seimetz D. (2010) Catumaxomab: clinical development and future directions. MAbs, 2 (2): 129-36. [PMID:20190561]

22. Linsley PS, Brady W, Urnes M, Grosmaire LS, Damle NK, Ledbetter JA. (1991) CTLA-4 is a second receptor for the B cell activation antigen B7. J. Exp. Med., 174 (3): 561-9. [PMID:1714933]

23. Liu Q. (2013) Fully human antibodies against human cd20. Patent number: WO2013007052. Assignee: Qingfa Liu. Priority date: 13/07/2011. Publication date: 17/01/2013.

24. Mitchell P. (2002) First biotech drug to treat psoriasis. Nat. Biotechnol., 20 (7): 640-1. [PMID:12089534]

25. Reslan L, Dalle S, Herveau S, Perrial E, Dumontet C. (2014) Apoptotic induction by anti-CD20 antibodies in chronic lymphocytic leukemia: comparison of rituximab and obinutuzumab. Leuk. Lymphoma, 55 (1): 188-90. [PMID:23537278]

26. Shitara K, Niwa R, Natsume A. (2011) Recombinant antibody composition. Patent number: US7923538 B2. Assignee: Kyowa Hakko Kirin Co., Ltd. Priority date: 22/07/2005. Publication date: 12/04/2011.

27. Simmons DL, Tan S, Tenen DG, Nicholson-Weller A, Seed B. (1989) Monocyte antigen CD14 is a phospholipid anchored membrane protein. Blood, 73 (1): 284-9. [PMID:2462937]

28. Stein R, Qu Z, Chen S, Rosario A, Shi V, Hayes M, Horak ID, Hansen HJ, Goldenberg DM. (2004) Characterization of a new humanized anti-CD20 monoclonal antibody, IMMU-106, and Its use in combination with the humanized anti-CD22 antibody, epratuzumab, for the therapy of non-Hodgkin's lymphoma. Clin. Cancer Res., 10 (8): 2868-78. [PMID:15102696]

29. Suchard SJ, Davis PM, Kansal S, Stetsko DK, Brosius R, Tamura J, Schneeweis L, Bryson J, Salcedo T, Wang H et al.. (2013) A monovalent anti-human CD28 domain antibody antagonist: preclinical efficacy and safety. J. Immunol., 191 (9): 4599-610. [PMID:24081989]

30. Suzuki K, Kumanogoh A, Kikutani H. (2008) Semaphorins and their receptors in immune cell interactions. Nat. Immunol., 9 (1): 17-23. [PMID:18087252]

31. van Deventer SJ, Dunlock VE, van Spriel AB. (2017) Molecular interactions shaping the tetraspanin web. Biochem. Soc. Trans., 45 (3): 741-750. [PMID:28620035]

32. Vicente Rabaneda EF, Herrero-Beaumont G, Castañeda S. (2013) Update on the use of abatacept for the treatment of rheumatoid arthritis. Expert Rev Clin Immunol, 9 (7): 599-621. [PMID:23899231]

33. Zhu L, Bergmeier W, Wu J, Jiang H, Stalker TJ, Cieslak M, Fan R, Boumsell L, Kumanogoh A, Kikutani H et al.. (2007) Regulated surface expression and shedding support a dual role for semaphorin 4D in platelet responses to vascular injury. Proc. Natl. Acad. Sci. U.S.A., 104 (5): 1621-6. [PMID:17244710]