Increasing tumor-infiltrating T cells through inhibition of CXCL12 with NOX-A12 synergizes with PD-1 blockade

Cancer Immunology Research

Volumn 5, Issue 11, 2017, Pages 950-956

  Zboralski, Dirk ^a,b   Hoehlig, Kai ^a,c   Eulberg, Dirk ^a   Frömming, Anna ^a   Vater, Axel ^a,c  

^a NOXXON PHARMA AG   (Germany)

^b Pharmaceuticals GmbH 3B   (Germany)

^c Aptarion Biotech   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; NOX A 12; OLAPTESED PEGOL; PROGRAMMED DEATH 1 INHIBITOR; PROGRAMMED DEATH 1 RECEPTOR; STROMAL CELL DERIVED FACTOR 1; UNCLASSIFIED DRUG; APTAMER; IMMUNOLOGICAL ANTINEOPLASTIC AGENT; NOX-A12;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; COLORECTAL CANCER; DRUG EFFICACY; DRUG POTENTIATION; FEMALE; HT-29 CELL LINE; IN VITRO STUDY; IN VIVO STUDY; MOUSE; MS-5 CELL LINE; NATURAL KILLER CELL; NONHUMAN; PSN1 CELL LINE; TUMOR ASSOCIATED LEUKOCYTE; TUMOR MICROENVIRONMENT; TUMOR SPHEROID; ANIMAL; ANTAGONISTS AND INHIBITORS; BAGG ALBINO MOUSE; COLON TUMOR; DRUG EFFECT; DRUG RESISTANCE; HUMAN; IMMUNOLOGY; PATHOLOGY; TUMOR CELL LINE;

ANIMALS; ANTINEOPLASTIC AGENTS, IMMUNOLOGICAL; APTAMERS, NUCLEOTIDE; CELL LINE, TUMOR; CHEMOKINE CXCL12; COLONIC NEOPLASMS; DRUG RESISTANCE, NEOPLASM; FEMALE; HUMANS; LYMPHOCYTES, TUMOR-INFILTRATING; MICE, INBRED BALB C; PROGRAMMED CELL DEATH 1 RECEPTOR; TUMOR MICROENVIRONMENT;

EID: 85033412051     PISSN: 23266066     EISSN: 23266074     Source Type: Journal    
DOI: 10.1158/2326-6066.CIR-16-0303     Document Type: Article

References (25)

1. Fridman WH, Pagès F, Sautès-Fridman C, Galon J. The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer 2012; 12:298–306.
2. Melero I, Rouzaut A, Motz GT, Coukos G. T-cell and NK-cell infiltration into solid tumors: a key limiting factor for efficacious cancer immunotherapy. Cancer Discov 2014;4:522–6.
3. Joyce JA, Fearon DT. T cell exclusion, immune privilege, and the tumor microenvironment. Science 2015;348:74–80.
4. Sharma P, Allison JP. The future of immune checkpoint therapy. Science 2015;348:56–61.
5. Guo F, Wang Y, Liu J, Mok SC, Xue F, Zhang W. CXCL12/CXCR4: a symbiotic bridge linking cancer cells and their stromal neighbors in oncogenic communication networks. Oncogene 2016;35:816–26.
6. Feig C, Jones JO, Kraman M, Wells RJ, Deonarine A, Chan DS, et al. Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizeswithanti–PD-L1immunotherapyinpancreaticcancer.ProcNatl Acad Sci U S A 2013;110:20212–7.
7. Fearon DT. The carcinoma-associated fibroblast expressing fibroblast activation protein and escape from immune surveillance. Cancer Immunol Res 2014;2:187–93.
8. Vater A, Klussmann S. Turning mirror-image oligonucleotides into drugs: the evolution of Spiegelmer therapeutics. Drug Discov Today 2015; 20:147–55.
9. Roccaro AM, Sacco A, Purschke WG, Moschetta M, Buchner K, Maasch C, et al. SDF-1 inhibition targets the bone marrow niche for cancer therapy. Cell Rep 2014;9:118–28.
10. Hoellenriegel J, Zboralski D, Maasch C, Rosin NY, Wierda WG, Keating MJ, et al. The Spiegelmer NOX-A12, a novel CXCL12 inhibitor, interferes with chronic lymphocytic leukemia cell motility and causes chemosensitization. Blood 2014;123:1032–9.
11. Liu SC, Alomran R, Chernikova SB, Lartey F, Stafford J, Jang T, et al. Blockade of SDF-1 after irradiation inhibits tumor recurrences of autochthonous brain tumors in rats. Neuro-oncology 2014;16:21–8.
12. Ludwig H, Weisel K, Petrucci MT, Leleu X, Cafro AM, Garderet L, et al. Olaptesed pegol, an anti-CXCL12/SDF-1 Spiegelmer, alone and with bortezomib-dexamethasone in relapsed/refractory multiple myeloma: a phase IIa study. Leukemia 2017;31:997–1000.
13. Steurer M, Montillo M, Scarfò L, Mauro FR, Andel J, Wildner S, et al. Results from a phase IIa study of the anti-CXCL12 spiegelmer olaptesed pegol (NOX-A12) in combination with bendamustine/rituximab in patients with chronic lymphocytic leukemia. Blood 2014;124:1996.
14. Chou TC. Drug combination studies and their synergy quantification using the Chou–Talalay method. Cancer Res 2010;70:440–6.
15. Mahoney KM, Rennert PD, Freeman GJ. Combination cancer immunotherapy and new immunomodulatory targets. Nat Rev Drug Discov 2015; 14:561–84.
16. Melero I, Berman DM, Aznar MA, Korman AJ, Pérez Gracia JL, Haanen J. Evolving synergistic combinations of targeted immunotherapies to combat cancer. Nat Rev Cancer 2015;15:457–72.
17. Giannattasio A, Weil S, Kloess S, Ansari N, Stelzer EH, Cerwenka A, et al. Cytotoxicity and infiltration of human NK cells in in vivo-like tumor spheroids. BMC Cancer 2015;15:351.
18. Santos AM, Jung J, Aziz N, Kissil JL, Puré E. Targeting fibroblast activation protein inhibits tumor stromagenesis and growth in mice. J Clin Invest 2009;119:3613–25.
19. Duraiswamy J, Kaluza KM, Freeman GJ, Coukos G. Dual blockade of PD-1 and CTLA-4 combined with tumor vaccine effectively restores T-cell rejection function in tumors. Cancer Res 2013;73:3591–603.
20. Callahan MK, Postow MA, Wolchok JD. CTLA-4 and PD-1 pathway blockade: combinations in the clinic. Front Oncol 2014;4:385.
21. Mellman I, Hubbard-Lucey VM, Tontonoz MJ, Kalos MD, Chen DS, Allison JP, et al. De-risking immunotherapy: report of a consensus workshop of the Cancer Immunotherapy Consortium of the Cancer Research Institute. Cancer Immunol Res 2016;4:279–88.
22. Boneschansker L, Yan J, Wong E, Briscoe DM, Irimia D. Microfluidic platform for the quantitative analysis of leukocyte migration signatures. Nat Commun 2014;5:4787.
23. Dunussi-Joannopoulos K, Zuberek K, Runyon K, Hawley RG, Wong A, Erickson J, et al. Efficacious immunomodulatory activity of the chemokine stromal cell-derived factor 1 (SDF-1): local secretion of SDF-1 at the tumor site serves as T-cell chemoattractant and mediates T-cell-dependent antitumor responses. Blood 2002;100:1551–8.
24. Poznansky MC, Olszak IT, Foxall R, Evans RH, Luster AD, Scadden DT. Active movement of T cells away from a chemokine. Nat Med 2000;6:543–8.
25. Chen Y, Ramjiawan RR, Reiberger T, Ng MR, Hato T, Huang Y, et al. CXCR4 inhibition in tumor microenvironment facilitates anti-programmed death receptor-1 immunotherapy in sorafenib-treated hepatocellular carcinoma in mice. Hepatology 2015;61:1591–602.