Skip to main content

Advertisement

SpringerLink
Log in

Targeting CTCFL/BORIS for the immunotherapy of cancer

  • Focussed Research Review
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Cancer vaccines have great potential in the fight against metastatic malignancies. Current anti-tumor immunotherapy is hindered by existing tolerance to tumor-associated antigens (TAA) and tumor escape using various mechanisms, highlighting the need for improved targets for immunotherapy. The cancer–testis antigen CTCFL/BORIS was discovered 16 years ago and possesses all features necessary for an ideal TAA. Recently CTCFL/BORIS has received additional attention as a target expressed in cancer stem cells (CSC). These cells drive tumor growth recurrence, metastasis, and treatment resistance. CTCFL/BORIS silencing leads to senescence and death of CSC. Therefore, an immunotherapeutic strategy that targets CTCFL/BORIS may lead to the selective destruction of CSC and potential eradication of metastatic disease. The high immunotherapeutic potential of CTCFL/BORIS antigen was shown in a stringent 4T1 mouse model of breast cancer. Using these highly metastatic, poorly immunogenic carcinoma cells inoculated into T-helper2 prone mice, we showed that DC fed with recombinant CTCFL/BORIS as an immunogen inhibited tumor growth and reduced the number of metastases in distant organs. About 20% of CTCFL/BORIS immunized animals were tumor free. 50% of animals remained metastasis free. Those having metastasis showed at least tenfold fewer metastases compared to controls. In a rat model of breast cancer, we showed that alphavirus-based CTCFL/BORIS immunotherapy was capable of cancer elimination as we were able to cure 50% of animals. Based on the above data, we believe that translation of CTCFL/BORIS-targeting immunotherapeutic strategies to the clinic will provide new avenues for improving survival of breast cancer patients with advanced metastatic disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

ABCG2:

ATP binding cassette subfamily G Member 2

ALDH1:

Aldehyde dehydrogenase 2

Alu:

Short human transposable element containing restriction site for the Alu enzyme

BMI1:

Putative oncogene belonging to the polycomb group

BORIS:

Brother of the regulator of imprinted sites

c-MYC:

Avian myelocytomatosis viral oncogene homolog

CD44:

Cluster of differentiation 44

CD47:

Cluster of differentiation 47

CFCE:

(5(6)-Carboxyfluorescein N-hydroxysuccinimidyl ester)

CSC:

Cancer stem cell

CTCF:

CTCC-binding factor

CTCFL:

CTCF-like

CTL:

Cytotoxic T-lymphocyte

HMG1:

High mobility group 1

hTERT:

Human telomerase (protein part)

LOH:

Loss of heterozygosity

MAGE-A1:

Melanoma antigen A1

MAGE-A3:

Melanoma antigen A3

MAGE-A6:

Melanoma Antigen A6

MDM2:

Mouse double minute 2 homolog

MHC:

Major histocompatibility complex

NANOG:

Homeobox transcription factor involved in ES cell pluripotency

NY-ESO:

Cancer–testis antigen found in SEREX screen for esophagus cancer

OCT4:

Octamer-binding transcription factor 4

p14ARF:

Alternative reading frame for INK4a

p16INK4a:

Inhibitor of CDK4, gene name CDKN2A

PDL-1:

Programmed death ligand-1

PDL-2:

Programmed death ligand-2

PIM1:

Putative proto-oncogene; Ser/Thr-kinase

PLK1:

Polo-like kinase 1

PRAME:

Preferentially expressed antigen in melanomas

Q-PCR:

Quantitative polymerase chain reaction

RPKM:

Reads per kilobase of transcripts per million mapped reads

RT-PCR:

Reverse transcription polymerase chain reaction

SINE:

Short interspersed nuclear element

SOX2:

SRY (sex determining region Y) box 2

TAA:

Tumor-associated antigen

VNTR:

Variable number tandem repeat

ZF-protein:

Zinc finger protein

References

  1. Lobanenkov VV, Nicolas RH, Adler VV, Paterson H, Klenova EM, Polotskaja AV, Goodwin GH (1990) A novel sequence-specific DNA binding protein which interacts with three regularly spaced direct repeats of the CCCTC-motif in the 5′-flanking sequence of the chicken c-myc gene. Oncogene 5(12):1743–1753

    CAS  PubMed  Google Scholar 

  2. Klenova EM, Nicolas RH, Paterson HF, Carne AF, Heath CM, Goodwin GH, Neiman PE, Lobanenkov VV (1993) CTCF, a conserved nuclear factor required for optimal transcriptional activity of the chicken c-myc gene, is an 11-Zn-finger protein differentially expressed in multiple forms. Mol Cell Biol 13(12):7612–7624

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Moon H, Filippova G, Loukinov D, Pugacheva E, Chen Q, Smith ST, Munhall A, Grewe B, Bartkuhn M, Arnold R, Burke LJ, Renkawitz-Pohl R, Ohlsson R, Zhou J, Renkawitz R, Lobanenkov V (2005) CTCF is conserved from Drosophila to humans and confers enhancer blocking of the Fab-8 insulator. EMBO Rep 6(2):165–170. https://doi.org/10.1038/sj.embor.7400334

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Phillips JE, Corces VG (2009) CTCF: master weaver of the genome. Cell 137(7):1194–1211. https://doi.org/10.1016/j.cell.2009.06.001

    Article  PubMed  PubMed Central  Google Scholar 

  5. Sanyal A, Lajoie BR, Jain G, Dekker J (2012) The long-range interaction landscape of gene promoters. Nature 489(7414):109–113. https://doi.org/10.1038/nature11279

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Rasko JE, Klenova EM, Leon J, Filippova GN, Loukinov DI, Vatolin S, Robinson AF, Hu YJ, Ulmer J, Ward MD, Pugacheva EM, Neiman PE, Morse HC 3rd, Collins SJ, Lobanenkov VV (2001) Cell growth inhibition by the multifunctional multivalent zinc-finger factor CTCF. Cancer Res 61(16):6002–6007

    CAS  PubMed  Google Scholar 

  7. Kanduri C, Pant V, Loukinov D, Pugacheva E, Qi CF, Wolffe A, Ohlsson R, Lobanenkov VV (2000) Functional association of CTCF with the insulator upstream of the H19 gene is parent of origin-specific and methylation-sensitive. Curr Biol 10(14):853–856

    Article  CAS  PubMed  Google Scholar 

  8. Filippova GN, Thienes CP, Penn BH, Cho DH, Hu YJ, Moore JM, Klesert TR, Lobanenkov VV, Tapscott SJ (2001) CTCF-binding sites flank CTG/CAG repeats and form a methylation-sensitive insulator at the DM1 locus. Nat Genet 28(4):335–343. https://doi.org/10.1038/ng570

    Article  CAS  PubMed  Google Scholar 

  9. Dixon JR, Selvaraj S, Yue F, Kim A, Li Y, Shen Y, Hu M, Liu JS, Ren B (2012) Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485(7398):376–380. https://doi.org/10.1038/nature11082

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Cuddapah S, Jothi R, Schones DE, Roh TY, Cui K, Zhao K (2009) Global analysis of the insulator binding protein CTCF in chromatin barrier regions reveals demarcation of active and repressive domains. Genome Res 19(1):24–32. https://doi.org/10.1101/gr.082800.108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Chao W, Huynh KD, Spencer RJ, Davidow LS, Lee JT (2002) CTCF, a candidate trans-acting factor for X-inactivation choice. Science 295(5553):345–347. https://doi.org/10.1126/science.1065982

    Article  CAS  PubMed  Google Scholar 

  12. Bell AC, West AG, Felsenfeld G (1999) The protein CTCF is required for the enhancer blocking activity of vertebrate insulators. Cell 98(3):387–396

    Article  CAS  PubMed  Google Scholar 

  13. Baniahmad A, Steiner C, Kohne AC, Renkawitz R (1990) Modular structure of a chicken lysozyme silencer: involvement of an unusual thyroid hormone receptor binding site. Cell 61(3):505–514

    Article  CAS  PubMed  Google Scholar 

  14. Splinter E, Heath H, Kooren J, Palstra RJ, Klous P, Grosveld F, Galjart N, de Laat W (2006) CTCF mediates long-range chromatin looping and local histone modification in the beta-globin locus. Genes Dev 20(17):2349–2354. https://doi.org/10.1101/gad.399506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Soshnikova N, Montavon T, Leleu M, Galjart N, Duboule D (2010) Functional analysis of CTCF during mammalian limb development. Dev Cell 19(6):819–830. https://doi.org/10.1016/j.devcel.2010.11.009

    Article  CAS  PubMed  Google Scholar 

  16. Heath H, Ribeiro de Almeida C, Sleutels F, Dingjan G, van de Nobelen S, Jonkers I, Ling KW, Gribnau J, Renkawitz R, Grosveld F, Hendriks RW, Galjart N (2008) CTCF regulates cell cycle progression of alphabeta T cells in the thymus. EMBO J 27(21):2839–2850. https://doi.org/10.1038/emboj.2008.214

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Amelio I, Melino G (2015) The p53 family and the hypoxia-inducible factors (HIFs): determinants of cancer progression. Trends Biochem Sci 40(8):425–434. https://doi.org/10.1016/j.tibs.2015.04.007

    Article  CAS  PubMed  Google Scholar 

  18. Al-Kaabi A, van Bockel LW, Pothen AJ, Willems SM (2014) p16INK4A and p14ARF gene promoter hypermethylation as prognostic biomarker in oral and oropharyngeal squamous cell carcinoma: a review. Dis Markers 2014:260549. https://doi.org/10.1155/2014/260549

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Reinhardt HC, Schumacher B (2012) The p53 network: cellular and systemic DNA damage responses in aging and cancer. Trends Genet 28(3):128–136. https://doi.org/10.1016/j.tig.2011.12.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Diederichs S, Bartsch L, Berkmann JC, Frose K, Heitmann J, Hoppe C, Iggena D, Jazmati D, Karschnia P, Linsenmeier M, Maulhardt T, Mohrmann L, Morstein J, Paffenholz SV, Ropenack P, Ruckert T, Sandig L, Schell M, Steinmann A, Voss G, Wasmuth J, Weinberger ME, Wullenkord R (2016) The dark matter of the cancer genome: aberrations in regulatory elements, untranslated regions, splice sites, non-coding RNA and synonymous mutations. EMBO Mol Med 8(5):442–457. https://doi.org/10.15252/emmm.201506055

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Jelinic P, Shaw P (2007) Loss of imprinting and cancer. J Pathol 211(3):261–268. https://doi.org/10.1002/path.2116

    Article  CAS  PubMed  Google Scholar 

  22. Uribe-Lewis S, Woodfine K, Stojic L, Murrell A (2011) Molecular mechanisms of genomic imprinting and clinical implications for cancer. Expert Rev Mol Med 13:e2. https://doi.org/10.1017/S1462399410001717

    Article  CAS  PubMed  Google Scholar 

  23. Chaligne R, Heard E (2014) X-chromosome inactivation in development and cancer. FEBS Lett 588(15):2514–2522. https://doi.org/10.1016/j.febslet.2014.06.023

    Article  CAS  PubMed  Google Scholar 

  24. Zink D, Fischer AH, Nickerson JA (2004) Nuclear structure in cancer cells. Nat Rev Cancer 4(9):677–687. https://doi.org/10.1038/nrc1430

    Article  CAS  PubMed  Google Scholar 

  25. Canela A, Maman Y, Jung S, Wong N, Callen E, Day A, Kieffer-Kwon KR, Pekowska A, Zhang H, Rao SSP, Huang SC, McKinnon PJ, Aplan PD, Pommier Y, Aiden EL, Casellas R, Nussenzweig A (2017) Genome organization drives chromosome fragility. Cell 170(3):507–521 e518. https://doi.org/10.1016/j.cell.2017.06.034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Filippova GN, Qi CF, Ulmer JE, Moore JM, Ward MD, Hu YJ, Loukinov DI, Pugacheva EM, Klenova EM, Grundy PE, Feinberg AP, Cleton-Jansen AM, Moerland EW, Cornelisse CJ, Suzuki H, Komiya A, Lindblom A, Dorion-Bonnet F, Neiman PE, Morse HC 3rd, Collins SJ, Lobanenkov VV (2002) Tumor-associated zinc finger mutations in the CTCF transcription factor selectively alter tts DNA-binding specificity. Cancer Res 62(1):48–52

    CAS  PubMed  Google Scholar 

  27. Loukinov DI, Pugacheva E, Vatolin S, Pack SD, Moon H, Chernukhin I, Mannan P, Larsson E, Kanduri C, Vostrov AA, Cui H, Niemitz EL, Rasko JE, Docquier FM, Kistler M, Breen JJ, Zhuang Z, Quitschke WW, Renkawitz R, Klenova EM, Feinberg AP, Ohlsson R, Morse HC 3rd, Lobanenkov VV (2002) BORIS, a novel male germ-line-specific protein associated with epigenetic reprogramming events, shares the same 11-zinc-finger domain with CTCF, the insulator protein involved in reading imprinting marks in the soma. Proc Natl Acad Sci USA 99(10):6806–6811. https://doi.org/10.1073/pnas.092123699

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Hore TA, Deakin JE, Marshall Graves JA (2008) The evolution of epigenetic regulators CTCF and BORIS/CTCFL in amniotes. PLoS Genet 4(8):e1000169. https://doi.org/10.1371/journal.pgen.1000169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Suzuki T, Kosaka-Suzuki N, Pack S, Shin DM, Yoon J, Abdullaev Z, Pugacheva E, Morse HC 3rd, Loukinov D, Lobanenkov V (2010) Expression of a testis-specific form of Gal3st1 (CST), a gene essential for spermatogenesis, is regulated by the CTCF paralogous gene BORIS. Mol Cell Biol 30(10):2473–2484. https://doi.org/10.1128/MCB.01093-09

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Sleutels F, Soochit W, Bartkuhn M, Heath H, Dienstbach S, Bergmaier P, Franke V, Rosa-Garrido M, van de Nobelen S, Caesar L, van der Reijden M, Bryne JC, van Ijcken W, Grootegoed JA, Delgado MD, Lenhard B, Renkawitz R, Grosveld F, Galjart N (2012) The male germ cell gene regulator CTCFL is functionally different from CTCF and binds CTCF-like consensus sites in a nucleosome composition-dependent manner. Epigenetics Chromatin 5(1):8. https://doi.org/10.1186/1756-8935-5-8

    Article  PubMed  PubMed Central  Google Scholar 

  31. Jones TA, Ogunkolade BW, Szary J, Aarum J, Mumin MA, Patel S, Pieri CA, Sheer D (2011) Widespread expression of BORIS/CTCFL in normal and cancer cells. Plos One. https://doi.org/10.1371/journal.pone.0022399 (ARTN e22399)

    Article  PubMed  PubMed Central  Google Scholar 

  32. Hines WC, Bazarov AV, Mukhopadhyay R, Yaswen P (2010) BORIS (CTCFL) is not expressed in most human breast cell lines and high grade breast carcinomas. PLoS One 5(3):e9738. https://doi.org/10.1371/journal.pone.0009738

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Sati L, Zeiss C, Yekkala K, Demir R, McGrath J (2015) Expression of the CTCFL gene during mouse embryogenesis causes growth retardation, postnatal lethality, and dysregulation of the transforming growth factor beta pathway. Mol Cell Biol 35(19):3436–3445. https://doi.org/10.1128/MCB.00381-15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Link PA, Zhang W, Odunsi K, Karpf AR (2013) BORIS/CTCFL mRNA isoform expression and epigenetic regulation in epithelial ovarian cancer. Cancer Immun 13:6

    PubMed  PubMed Central  Google Scholar 

  35. Risinger JI, Chandramouli GV, Maxwell GL, Custer M, Pack S, Loukinov D, Aprelikova O, Litzi T, Schrump DS, Murphy SK, Berchuck A, Lobanenkov V, Barrett JC (2007) Global expression analysis of cancer/testis genes in uterine cancers reveals a high incidence of BORIS expression. Clin Cancer Res 13(6):1713–1719. https://doi.org/10.1158/1078-0432.CCR-05-2569

    Article  CAS  PubMed  Google Scholar 

  36. D’Arcy V, Pore N, Docquier F, Abdullaev ZK, Chernukhin I, Kita GX, Rai S, Smart M, Farrar D, Pack S, Lobanenkov V, Klenova E (2008) BORIS, a paralogue of the transcription factor, CTCF, is aberrantly expressed in breast tumours. Br J Cancer 98(3):571–579. https://doi.org/10.1038/sj.bjc.6604181

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. de Necochea-Campion R, Ghochikyan A, Josephs SF, Zacharias S, Woods E, Karimi-Busheri F, Alexandrescu DT, Chen CS, Agadjanyan MG, Carrier E (2011) Expression of the epigenetic factor BORIS (CTCFL) in the human genome. J Transl Med 9:213. https://doi.org/10.1186/1479-5876-9-213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Wang C, Gu Y, Zhang K, Xie K, Zhu M, Dai N, Jiang Y, Guo X, Liu M, Dai J, Wu L, Jin G, Ma H, Jiang T, Yin R, Xia Y, Liu L, Wang S, Shen B, Huo R, Wang Q, Xu L, Yang L, Huang X, Shen H, Sha J, Hu Z (2016) Systematic identification of genes with a cancer–testis expression pattern in 19 cancer types. Nat Commun 7:10499. https://doi.org/10.1038/ncomms10499

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Pugacheva EM, Suzuki T, Pack SD, Kosaka-Suzuki N, Yoon J, Vostrov AA, Barsov E, Strunnikov AV, Morse HC 3rd, Loukinov D, Lobanenkov V (2010) The structural complexity of the human BORIS gene in gametogenesis and cancer. PLoS One 5(11):e13872. https://doi.org/10.1371/journal.pone.0013872

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Pugacheva EM, Rivero-Hinojosa S, Espinoza CA, Mendez-Catala CF, Kang S, Suzuki T, Kosaka-Suzuki N, Robinson S, Nagarajan V, Ye Z, Boukaba A, Rasko JE, Strunnikov AV, Loukinov D, Ren B, Lobanenkov VV (2015) Comparative analyses of CTCF and BORIS occupancies uncover two distinct classes of CTCF binding genomic regions. Genome Biol 16:161. https://doi.org/10.1186/s13059-015-0736-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Pugacheva EM, Teplyakov E, Wu Q, Li J, Chen C, Meng C, Liu J, Robinson S, Loukinov D, Boukaba A, Hutchins AP, Lobanenkov V, Strunnikov A (2016) The cancer-associated CTCFL/BORIS protein targets multiple classes of genomic repeats, with a distinct binding and functional preference for humanoid-specific SVA transposable elements. Epigenetics Chromatin 9(1):35. https://doi.org/10.1186/s13072-016-0084-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Reya T, Morrison SJ, Clarke MF, Weissman IL (2001) Stem cells, cancer, and cancer stem cells. Nature 414(6859):105–111. https://doi.org/10.1038/35102167

    Article  CAS  PubMed  Google Scholar 

  43. Dalerba P, Cho RW, Clarke MF (2007) Cancer stem cells: models and concepts. Annu Rev Med 58:267–284. https://doi.org/10.1146/annurev.med.58.062105.204854

    Article  CAS  PubMed  Google Scholar 

  44. Jordan CT, Guzman ML, Noble M (2006) Cancer stem cells. N Engl J Med 355(12):1253–1261. https://doi.org/10.1056/NEJMra061808

    Article  CAS  PubMed  Google Scholar 

  45. Alberti L, Renaud S, Losi L, Leyvraz S, Benhattar J (2014) High expression of hTERT and stemness genes in BORIS/CTCFL positive cells isolated from embryonic cancer cells. PLoS One 9(10):e109921. https://doi.org/10.1371/journal.pone.0109921

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Alberti L, Losi L, Leyvraz S, Benhattar J (2015) Different effects of BORIS/CTCFL on stemness gene expression, sphere formation and cell survival in epithelial cancer stem cells. PLoS One 10(7):e0132977. https://doi.org/10.1371/journal.pone.0132977

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Asano T, Hirohashi Y, Torigoe T, Mariya T, Horibe R, Kuroda T, Tabuchi Y, Saijo H, Yasuda K, Mizuuchi M, Takahashi A, Asanuma H, Hasegawa T, Saito T, Sato N (2016) Brother of the regulator of the imprinted site (BORIS) variant subfamily 6 is involved in cervical cancer stemness and can be a target of immunotherapy. Oncotarget 7(10):11223–11237. https://doi.org/10.18632/oncotarget.7165

    Article  PubMed  PubMed Central  Google Scholar 

  48. Mkrtichyan M, Ghochikyan A, Loukinov D, Davtyan H, Ichim TE, Cribbs DH, Lobanenkov VV, Agadjanyan MG (2008) DNA, but not protein vaccine based on mutated BORIS antigen significantly inhibits tumor growth and prolongs the survival of mice. Gene Ther 15(1):61–64. https://doi.org/10.1038/sj.gt.3303044

    Article  CAS  PubMed  Google Scholar 

  49. Horibe R, Hirohashi Y, Asano T, Mariya T, Suzuki T, Takaya A, Saijo H, Shionoya Y, Kubo T, Nakatsugawa M, Kanaseki T, Tsukahara T, Watanabe K, Atsuyama E, Toji S, Hirano H, Hasegawa T, Takahashi H, Sato N, Torigoe T (2017) Brother of the regulator of the imprinted site (BORIS) variant subfamily 6 is a novel target of lung cancer stem-like cell immunotherapy. PLoS One 12(3):e0171460. https://doi.org/10.1371/journal.pone.0171460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Garikapati KR, Patel N, Makani VK, Cilamkoti P, Bhadra U, Bhadra MP (2017) Down-regulation of BORIS/CTCFL efficiently regulates cancer stemness and metastasis in MYCN amplified neuroblastoma cell line by modulating Wnt/beta-catenin signaling pathway. Biochem Biophys Res Commun 484(1):93–99. https://doi.org/10.1016/j.bbrc.2017.01.066

    Article  CAS  PubMed  Google Scholar 

  51. Smith IM, Glazer CA, Mithani SK, Ochs MF, Sun W, Bhan S, Vostrov A, Abdullaev Z, Lobanenkov V, Gray A, Liu C, Chang SS, Ostrow KL, Westra WH, Begum S, Dhara M, Califano J, Najbauer J (2009) Coordinated activation of candidate proto-oncogenes and cancer testes antigens via promoter demethylation in head and neck cancer and lung cancer. PLoS ONE 4(3):e4961

    Article  PubMed  PubMed Central  Google Scholar 

  52. Loukinov D, Ghochikyan A, Mkrtichyan M, Ichim TE, Lobanenkov VV, Cribbs DH, Agadjanyan MG (2006) Antitumor efficacy of DNA vaccination to the epigenetically acting tumor promoting transcription factor BORIS and CD80 molecular adjuvant. J Cell Biochem 98(5):1037–1043. https://doi.org/10.1002/jcb.20953

    Article  CAS  PubMed  Google Scholar 

  53. Ghochikyan A, Mkrtichyan M, Loukinov D, Mamikonyan G, Pack SD, Movsesyan N, Ichim TE, Cribbs DH, Lobanenkov VV, Agadjanyan MG (2007) Elicitation of T cell responses to histologically unrelated tumors by immunization with the novel cancer–testis antigen, brother of the regulator of imprinted sites. J Immunol 178(1):566–573

    Article  CAS  PubMed  Google Scholar 

  54. Mkrtichyan M, Ghochikyan A, Davtyan H, Movsesyan N, Loukinov D, Lobanenkov V, Cribbs DH, Laust AK, Nelson EL, Agadjanyan MG (2011) Cancer–testis antigen, BORIS based vaccine delivered by dendritic cells is extremely effective against a very aggressive and highly metastatic mouse mammary carcinoma. Cell Immunol 270(2):188–197. https://doi.org/10.1016/j.cellimm.2011.05.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Author would like to thank Susan Robinson and Sandy Morse III for helping with editing the manuscript.

Funding

This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health.

Author information

Authors and Affiliations

  1. Molecular Pathology Section, Laboratory of Immunogenetics, NIAID/NIH, Twinbrook 1, Room 1329, 5640 Fishers Lane, Rockville, MD, 20852, USA

    Dmitri Loukinov

Authors
  1. Dmitri Loukinov
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dmitri Loukinov.

Ethics declarations

Conflict of interest

The author has no conflict of interests to declare.

Additional information

This paper is a Focussed Research Review based on a presentation given at the Fifth International Conference on Cancer Immunotherapy and Immunomonitoring (CITIM 2017), held in Prague, Czech Republic, 24th–27th April 2017. It is part of a series of Focussed Research Reviews and meeting report in Cancer Immunology, Immunotherapy.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Loukinov, D. Targeting CTCFL/BORIS for the immunotherapy of cancer. Cancer Immunol Immunother 67, 1955–1965 (2018). https://doi.org/10.1007/s00262-018-2251-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00262-018-2251-8

Keywords

Search

Navigation