Skip to main content
SpringerLink
Log in

p53 Immunotherapy of Cancer

  • Chapter
  • First Online:
p53 in the Clinics

  • 1042 Accesses

Abstract

Mutation and overexpression of the p53 tumor suppressor protein are the most common genetic alterations in human cancers. Peptides derived from non-mutated (wild type, wt) and mutated p53-molecules, processed and presented in the context of major histocompatibility complex (MHC) molecules by tumor cells for T-cell recognition, could serve as broad targets for cancer immunotherapy. Isolating p53-reactive T lymphocytes in healthy donors or patients has been hampered by the fact that most individuals display a peripheral p53-reactive T-cell repertoire that is devoid of high-avidity MHC class I-restricted cytotoxic T lymphocytes (CTL). Only low-avidity T lymphocytes are left due to self-tolerance to this ubiquitously expressed molecule. The transfer into T cells of T-cell antigen receptor (TCR) genes encoding high-affinity TCRs and recognizing defined tumor-associated antigens can circumvent these hurdles. Delivery of a high-affinity CD8-independent, p53-specific TCR into human T cells offers an exciting strategy to redirect CD8+ T lymphocytes with broad tumor-specific CTL activity and turn CD4+ T cells into potent tumor-reactive, p53-specific T helper (Th) cells. Adoptive transfer of p53 TCR-engineered human lymphocytes offers a novel approach for a broad-spectrum immunotherapy of malignant disease.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Albers AE, Ferris RL, Kim GG, Chikamatsu K, DeLeo AB, Whiteside TL (2005) Immune responses to p53 in patients with cancer: enrichment in tetramer  +  p53 peptide-specific T cells and regulatory T cells at tumor sites. Cancer Immunol Immunother 54:1072–1081

    Article  PubMed  CAS  Google Scholar 

  • Antonia SJ, Mirza N, Fricke I, Chiappori A, Thompson P, Williams N, Bepler G, Simon G, Janssen W, Lee JH, Menander K, Chada S, Gabrilovich DI (2006) Combination of p53 cancer vaccine with chemotherapy in patients with extensive stage small cell lung cancer. Clin Cancer Res 12:878–887

    Article  PubMed  CAS  Google Scholar 

  • Ashcroft M, Vousden KH (1999) Regulation of p53 stability. Oncogene 18:7637–7643

    Article  PubMed  CAS  Google Scholar 

  • Bendle GM, Linnemann C, Hooijkaas AI, Bies L, de Witte MA, Jorritsma A, Kaiser AD, Pouw N, Debets R, Kieback E, Uckert W, Song JY, Haanen JB, Schumacher TN (2010) Lethal graft-versus-host disease in mouse models of T cell receptor gene therapy. Nat Med 16(565–70):1p

    Google Scholar 

  • Bennett SR, Carbone FR, Karamalis F, Flavell RA, Miller JF, Heath WR (1998) Help for cytotoxic-T-cell responses is mediated by CD40 signalling. Nature 393:478–480

    Article  PubMed  CAS  Google Scholar 

  • Berger C, Jensen MC, Lansdorp PM, Gough M, Elliott C, Riddell SR (2008) Adoptive transfer of effector CD8+ T cells derived from central memory cells establishes persistent T cell memory in primates. J Clin Invest 118:294–305

    Article  PubMed  CAS  Google Scholar 

  • Bos R, Sherman LA (2010) CD4+ T-cell help in the tumor milieu is required for recruitment and cytolytic function of CD8+ T lymphocytes. Cancer Res 70:8368–8377

    Article  PubMed  CAS  Google Scholar 

  • Carbone DP, Ciernik IF, Kelley MJ, Smith MC, Nadaf S, Kavanaugh D, Maher VE, Stipanov M, Contois D, Johnson BE, Pendleton CD, Seifert B, Carter C, Read EJ, Greenblatt J, Top LE, Kelsey MI, Minna JD, Berzofsky JA (2005) Immunization with mutant p53- and K-ras-derived peptides in cancer patients: immune response and clinical outcome. J Clin Oncol 23:5099–5107

    Article  PubMed  Google Scholar 

  • Chikamatsu K, Albers A, Stanson J, Kwok WW, Appella E, Whiteside TL, DeLeo AB (2003) P53(110-124)-specific human CD4+ T-helper cells enhance in vitro generation and antitumor function of tumor-reactive CD8+ T cells. Cancer Res 63:3675–3681

    PubMed  CAS  Google Scholar 

  • Cohen CJ, Zheng Z, Bray R, Zhao Y, Sherman LA, Rosenberg SA, Morgan RA (2005) Recognition of fresh human tumor by human peripheral blood lymphocytes transduced with a bicistronic retroviral vector encoding a murine anti-p53 TCR. J Immunol 175:5799–5808

    PubMed  CAS  Google Scholar 

  • Cohen CJ, Zhao Y, Zheng Z, Rosenberg SA, Morgan RA (2006) Enhanced antitumor activity of murine-human hybrid T-cell receptor (TCR) in human lymphocytes is associated with improved pairing and TCR/CD3 stability. Cancer Res 66:8878–8886

    Article  PubMed  CAS  Google Scholar 

  • Davis JL, Theoret MR, Zheng Z, Lamers CH, Rosenberg SA, Morgan RA (2010) Development of human anti-murine T-cell receptor antibodies in both responding and nonresponding patients enrolled in TCR gene therapy trials. Clin Cancer Res 16:5852–5861

    Article  PubMed  CAS  Google Scholar 

  • de Witte MA, Jorritsma A, Kaiser A, van den Boom MD, Dokter M, Bendle GM, Haanen JB, Schumacher TN (2008) Requirements for effective antitumor responses of TCR transduced T cells. J Immunol 181:5128–5136

    PubMed  Google Scholar 

  • Fedoseyeva EV, Boisgerault F, Anosova NG, Wollish WS, Arlotta P, Jensen PE, Ono SJ, Benichou G (2000) CD4+ T cell responses to self- and mutated p53 determinants during tumorigenesis in mice. J Immunol 164:5641–5651

    PubMed  CAS  Google Scholar 

  • Fujita H, Senju S, Yokomizo H, Saya H, Ogawa M, Matsushita S, Nishimura Y (1998) Evidence that HLA class II-restricted human CD4+ T cells specific to p53 self peptides respond to p53 proteins of both wild and mutant forms. Eur J Immunol 28:305–316

    Article  PubMed  CAS  Google Scholar 

  • Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70

    Article  PubMed  CAS  Google Scholar 

  • Haupt Y, Maya R, Kazaz A, Oren M (1997) Mdm2 promotes the rapid degradation of p53. Nature 387:296–299

    Article  PubMed  CAS  Google Scholar 

  • Heath WR, Kurts C, Miller JF, Carbone FR (1998) Cross-tolerance: a pathway for inducing tolerance to peripheral tissue antigens. J Exp Med 187:1549–1553

    Article  PubMed  CAS  Google Scholar 

  • Hernandez J, Lee PP, Davis MM, Sherman LA (2000) The use of HLA A2.1/p53 peptide tetramers to visualize the impact of self tolerance on the TCR repertoire. J Immunol 164:596–602

    PubMed  CAS  Google Scholar 

  • Hernandez J, Ko A, Sherman LA (2001) CTLA-4 blockade enhances the CTL responses to the p53 self-tumor antigen. J Immunol 166:3908–3914

    PubMed  CAS  Google Scholar 

  • Hilburger RM, Abrams SI (2001) Characterization of CD8+ cytotoxic T lymphocyte/tumor cell interactions reflecting recognition of an endogenously expressed murine wild-type p53 determinant. Cancer Immunol Immunother 49:603–612

    Article  Google Scholar 

  • Hinrichs CS, Borman ZA, Cassard L, Gattinoni L, Spolski R, Yu Z, Sanchez-Perez L, Muranski P, Kern SJ, Logun C, Palmer DC, Ji Y, Reger RN, Leonard WJ, Danner RL, Rosenberg SA, Restifo NP (2009) Adoptively transferred effector cells derived from naive rather than central memory CD8+ T cells mediate superior antitumor immunity. Proc Natl Acad Sci USA 106:17469–17474

    Article  PubMed  CAS  Google Scholar 

  • Hoffmann TK, Nakano K, Elder EM, Dworacki G, Finkelstein SD, Appella E, Whiteside TL, DeLeo AB (2000) Generation of T cells specific for the wild-type sequence p53(264-272) peptide in cancer patients: implications for immunoselection of epitope loss variants. J Immunol 165:5938–5944

    PubMed  CAS  Google Scholar 

  • Hoffmann TK, Donnenberg AD, Finkelstein SD, Donnenberg VS, Friebe-Hoffmann U, Myers EN, Appella E, DeLeo AB, Whiteside TL (2002) Frequencies of tetramer  +  T cells specific for the wild-type sequence p53(264-272) peptide in the circulation of patients with head and neck cancer. Cancer Res 62:3521–3529

    PubMed  CAS  Google Scholar 

  • Hollstein M, Sidransky D, Vogelstein B, Harris CC (1991) p53 mutations in human cancers. Science 253:49–53

    Article  PubMed  CAS  Google Scholar 

  • Hung K, Hayashi R, Lafond-Walker A, Lowenstein C, Pardoll D, Levitsky H (1998) The central role of CD4(+) T cells in the antitumor immune response. J Exp Med 188:2357–2368

    Article  PubMed  CAS  Google Scholar 

  • Ito D, Albers A, Zhao YX, Visus C, Appella E, Whiteside TL, DeLeo AB (2006) The wild-type sequence (wt) p53(25-35) peptide induces HLA-DR7 and HLA-DR11-restricted CD4+ Th cells capable of enhancing the ex vivo expansion and function of anti-wt p53(264-272) peptide CD8+ T cells. J Immunol 177:6795–6803

    PubMed  CAS  Google Scholar 

  • Ito D, Visus C, Hoffmann TK, Balz V, Bier H, Appella E, Whiteside TL, Ferris RL, DeLeo AB (2007) Immunological characterization of missense mutations occurring within cytotoxic T cell-defined p53 epitopes in HLA-A*0201+ squamous cell carcinomas of the head and neck. Int J Cancer 120:2618–2624

    Article  PubMed  CAS  Google Scholar 

  • Kuball J, Schuler M, Antunes FE, Herr W, Neumann M, Obenauer-Kutner L, Westreich L, Huber C, Wolfel T, Theobald M (2002) Generating p53-specific cytotoxic T lymphocytes by recombinant adenoviral vector-based vaccination in mice, but not man. Gene Ther 9:833–843

    Article  PubMed  CAS  Google Scholar 

  • Kuball J, Schmitz FW, Voss RH, Ferreira EA, Engel R, Guillaume P, Strand S, Romero P, Huber C, Sherman LA, Theobald M (2005) Cooperation of human tumor-reactive CD4+ and CD8+ T cells after redirection of their specificity by a high-affinity p53A2.1-specific TCR. Immunity 22:117–129

    Article  PubMed  CAS  Google Scholar 

  • Kuball J, Dossett ML, Wolfl M, Ho WY, Voss RH, Fowler C, Greenberg PD (2007) Facilitating matched pairing and expression of TCR chains introduced into human T cells. Blood 109:2331–2338

    Article  PubMed  CAS  Google Scholar 

  • Kuball J, Hauptrock B, Malina V, Antunes E, Voss RH, Wolfl M, Strong R, Theobald M, Greenberg PD (2009) Increasing functional avidity of TCR-redirected T cells by removing defined N-glycosylation sites in the TCR constant domain. J Exp Med 206:463–475

    Article  PubMed  CAS  Google Scholar 

  • Kubbutat MH, Jones SN, Vousden KH (1997) Regulation of p53 stability by Mdm2. Nature 387:299–303

    Article  PubMed  CAS  Google Scholar 

  • Kuckelkorn U, Ferreira EA, Drung I, Liewer U, Kloetzel PM, Theobald M (2002) The effect of the interferon-gamma-inducible processing machinery on the generation of a naturally tumor-associated human cytotoxic T lymphocyte epitope within a wild-type and mutant p53 sequence context. Eur J Immunol 32:1368–1375

    Article  PubMed  CAS  Google Scholar 

  • Lambeck A, Leffers N, Hoogeboom BN, Sluiter W, Hamming I, Klip H, ten Hoor K, Esajas M, van Oven M, Drijfhout JW, Platteel I, Offringa R, Hollema H, Melief K, van der Burg S, van der Zee A, Daemen T, Nijman H (2007) P53-specific T cell responses in patients with malignant and benign ovarian tumors: implications for p53 based immunotherapy. Int J Cancer 121:606–614

    Article  PubMed  CAS  Google Scholar 

  • Lauwen MM, Zwaveling S, de Quartel L, Ferreira Mota SC, Grashorn JA, Melief CJ, van der Burg SH, Offringa R (2008) Self-tolerance does not restrict the CD4+ T-helper response against the p53 tumor antigen. Cancer Res 68:893–900

    Article  PubMed  CAS  Google Scholar 

  • Lee KH, Wang E, Nielsen MB, Wunderlich J, Migueles S, Connors M, Steinberg SM, Rosenberg SA, Marincola FM (1999) Increased vaccine-specific T cell frequency after peptide-based vaccination correlates with increased susceptibility to in vitro stimulation but does not lead to tumor regression. J Immunol 163:6292–6300

    PubMed  CAS  Google Scholar 

  • Leffers N, Lambeck AJ, Gooden MJ, Hoogeboom BN, Wolf R, Hamming IE, Hepkema BG, Willemse PH, Molmans BH, Hollema H, Drijfhout JW, Sluiter WJ, Valentijn AR, Fathers LM, Oostendorp J, van der Zee AG, Melief CJ, van der Burg SH, Daemen T, Nijman HW (2009) Immunization with a P53 synthetic long peptide vaccine induces P53-specific immune responses in ovarian cancer patients, a phase II trial. Int J Cancer 125:2104–2113

    Article  PubMed  CAS  Google Scholar 

  • Luo JL, Yang Q, Tong WM, Hergenhahn M, Wang ZQ, Hollstein M (2001) Knock-in mice with a chimeric human/murine p53 gene develop normally and show wild-type p53 responses to DNA damaging agents: a new biomedical research tool. Oncogene 20:320–328

    Article  PubMed  CAS  Google Scholar 

  • Morgan RA, Dudley ME, Wunderlich JR, Hughes MS, Yang JC, Sherry RM, Royal RE, Topalian SL, Kammula US, Restifo NP, Zheng Z, Nahvi A, de Vries CR, Rogers-Freezer LJ, Mavroukakis SA, Rosenberg SA (2006) Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 314:126–129

    Article  PubMed  CAS  Google Scholar 

  • Nikitina EY, Chada S, Muro-Cacho C, Fang B, Zhang R, Roth JA, Gabrilovich DI (2002) An effective immunization and cancer treatment with activated dendritic cells transduced with full-length wild-type p53. Gene Ther 9:345–352

    Article  PubMed  CAS  Google Scholar 

  • Noguchi Y, Chen YT, Old LJ (1994) A mouse mutant p53 product recognized by CD4+ and CD8+ T cells. Proc Natl Acad Sci USA 91:3171–3175

    Article  PubMed  CAS  Google Scholar 

  • Peralta EA, Liu X, McCarthy TM, Wilson TG, Diamond DJ, Ellenhorn JD (1999) Immunotherapy of bladder cancer targeting P53. J Urol 162:1806–1811

    Article  PubMed  CAS  Google Scholar 

  • Ridge JP, Di Rosa F, Matzinger P (1998) A conditioned dendritic cell can be a temporal bridge between a CD4+ T-helper and a T-killer cell. Nature 393:474–478

    Article  PubMed  CAS  Google Scholar 

  • Robbins PF, Dudley ME, Wunderlich J, El Gamil M, Li YF, Zhou J, Huang J, Powell DJ Jr, Rosenberg SA (2004) Cutting edge: persistence of transferred lymphocyte clonotypes correlates with cancer regression in patients receiving cell transfer therapy. J Immunol 173:7125–7130

    PubMed  CAS  Google Scholar 

  • Robinson CR, Sauer RT (1998) Optimizing the stability of single-chain proteins by linker length and composition mutagenesis. Proc Natl Acad Sci USA 95:5929–5934

    Article  PubMed  CAS  Google Scholar 

  • Rogel A, Popliker M, Webb CG, Oren M (1985) p53 cellular tumor antigen: analysis of mRNA levels in normal adult tissues, embryos, and tumors. Mol Cell Biol 5:2851–2855

    PubMed  CAS  Google Scholar 

  • Sallusto F, Lenig D, Forster R, Lipp M, Lanzavecchia A (1999) Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature 401:708–712

    Article  PubMed  CAS  Google Scholar 

  • Scheffner M, Huibregtse JM, Vierstra RD, Howley PM (1993) The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53. Cell 75:495–505

    Article  PubMed  CAS  Google Scholar 

  • Schoenberger SP, Toes RE, van der Voort EI, Offringa R, Melief CJ (1998) T-cell help for cytotoxic T lymphocytes is mediated by CD40-CD40L interactions. Nature 393:480–483

    Article  PubMed  CAS  Google Scholar 

  • Scholten KB, Kramer D, Kueter EW, Graf M, Schoedl T, Meijer CJ, Schreurs MW, Hooijberg E (2006) Codon modification of T cell receptors allows enhanced functional expression in transgenic human T cells. Clin Immunol 119:135–145

    Article  PubMed  CAS  Google Scholar 

  • Schumacher TN (2002) T-cell-receptor gene therapy. Nat Rev Immunol 2:512–519

    Article  PubMed  CAS  Google Scholar 

  • Sherman LA, Hesse SV, Irwin MJ, La Face D, Peterson P (1992) Selecting T cell receptors with high affinity for self-MHC by decreasing the contribution of CD8. Science 258:815–818

    Article  PubMed  CAS  Google Scholar 

  • Song GY, Gibson G, Haq W, Huang EC, Srivasta T, Hollstein M, Daftarian P, Wang Z, Diamond D, Ellenhorn JD (2007) An MVA vaccine overcomes tolerance to human p53 in mice and humans. Cancer Immunol Immunother 56:1193–1205

    Article  PubMed  CAS  Google Scholar 

  • Speetjens FM, Kuppen PJ, Welters MJ, Essahsah F, Voet van den Brink AM, Lantrua MG, Valentijn AR, Oostendorp J, Fathers LM, Nijman HW, Drijfhout JW, van de Velde CJ, Melief CJ, van der Burg SH (2009) Induction of p53-specific immunity by a p53 synthetic long peptide vaccine in patients treated for metastatic colorectal cancer. Clin Cancer Res 15:1086–1095

    Article  PubMed  CAS  Google Scholar 

  • Stanislawski T, Voss RH, Lotz C, Sadovnikova E, Willemsen RA, Kuball J, Ruppert T, Bolhuis RL, Melief CJ, Huber C, Stauss HJ, Theobald M (2001) Circumventing tolerance to a human MDM2-derived tumor antigen by TCR gene transfer. Nat Immunol 2:962–970

    Article  PubMed  CAS  Google Scholar 

  • Svane IM, Pedersen AE, Nikolajsen K, Zocca MB (2008) Alterations in p53-specific T cells and other lymphocyte subsets in breast cancer patients during vaccination with p53-peptide loaded dendritic cells and low-dose interleukin-2. Vaccine 26:4716–4724

    Article  PubMed  CAS  Google Scholar 

  • Theobald M, Biggs J, Dittmer D, Levine AJ, Sherman LA (1995) Targeting p53 as a general tumor antigen. Proc Natl Acad Sci USA 92:11993–11997

    Article  PubMed  CAS  Google Scholar 

  • Theobald M, Biggs J, Hernandez J, Lustgarten J, Labadie C, Sherman LA (1997) Tolerance to p53 by A2.1-restricted cytotoxic T lymphocytes. J Exp Med 185:833–841

    Article  PubMed  CAS  Google Scholar 

  • Theobald M, Ruppert T, Kuckelkorn U, Hernandez J, Haussler A, Ferreira EA, Liewer U, Biggs J, Levine AJ, Huber C, Koszinowski UH, Kloetzel PM, Sherman LA (1998) The sequence alteration associated with a mutational hotspot in p53 protects cells from lysis by cytotoxic T lymphocytes specific for a flanking peptide epitope. J Exp Med 188:1017–1028

    Article  PubMed  CAS  Google Scholar 

  • van der Burg SH, Menon AG, Redeker A, Franken KL, Drijfhout JW, Tollenaar RA, Hartgrink HH, van de Velde CJ, Kuppen PJ, Melief CJ, Offringa R (2003) Magnitude and polarization of P53-specific T-helper immunity in connection to leukocyte infiltration of colorectal tumors. Int J Cancer 107:425–433

    Article  PubMed  Google Scholar 

  • Vierboom MP, Nijman HW, Offringa R, van der Voort EI, van Hall T, van den Broek L, Fleuren GJ, Kenemans P, Kast WM, Melief CJ (1997) Tumor eradication by wild-type p53-specific cytotoxic T lymphocytes. J Exp Med 186:695–704

    Article  PubMed  CAS  Google Scholar 

  • Vierboom MP, Zwaveling S, Bos GMJ, Ooms M, Krietemeijer GM, Melief CJ, Offringa R (2000) High steady-state levels of p53 are not a prerequisite for tumor eradication by wild-type p53-specific cytotoxic T lymphocytes. Cancer Res 60:5508–5513

    PubMed  CAS  Google Scholar 

  • Voss RH, Willemsen RA, Kuball J, Grabowski M, Engel R, Intan RS, Guillaume P, Romero P, Huber C, Theobald M (2008) Molecular design of the Calphabeta interface favors specific pairing of introduced TCRalphabeta in human T cells. J Immunol 180:391–401

    PubMed  CAS  Google Scholar 

  • Voss RH, Thomas S, Pfirschke C, Hauptrock B, Klobuch S, Kuball J, Grabowski M, Engel R, Guillaume P, Romero P, Huber C, Beckhove P, Theobald M (2010) Coexpression of the T-cell receptor constant alpha domain triggers tumor reactivity of single-chain TCR-transduced human T cells. Blood 115:5154–5163

    Article  PubMed  CAS  Google Scholar 

  • Walker LS, Abbas AK (2002) The enemy within: keeping self-reactive T cells at bay in the periphery. Nat Rev Immunol 2:11–19

    Article  PubMed  CAS  Google Scholar 

  • Wong SB, Bos R, Sherman LA (2008) Tumor-specific CD4+ T cells render the tumor environment permissive for infiltration by low-avidity CD8+ T cells. J Immunol 180:3122–3131

    PubMed  CAS  Google Scholar 

  • Xie Y, Akpinarli A, Maris C, Hipkiss EL, Lane M, Kwon EK, Muranski P, Restifo NP, Antony PA (2010) Naive tumor-specific CD4(+) T cells differentiated in vivo eradicate established melanoma. J Exp Med 207:651–667

    Article  PubMed  CAS  Google Scholar 

  • Xue SA, Gao L, Hart D, Gillmore R, Qasim W, Thrasher A, Apperley J, Engels B, Uckert W, Morris E, Stauss H (2005) Elimination of human leukemia cells in NOD/SCID mice by WT1-TCR gene-transduced human T cells. Blood 106:3062–3067

    Article  PubMed  CAS  Google Scholar 

  • Yanuck M, Carbone DP, Pendleton CD, Tsukui T, Winter SF, Minna JD, Berzofsky JA (1993) A mutant p53 tumor suppressor protein is a target for peptide-induced CD8+ cytotoxic T-cells. Cancer Res 53:3257–3261

    PubMed  CAS  Google Scholar 

  • Zwaveling S, Vierboom MP, Ferreira Mota SC, Hendriks JA, Ooms ME, Sutmuller RP, Franken KL, Nijman HW, Ossendorp F, van der Burg SH, Offringa R, Melief CJ (2002) Antitumor efficacy of wild-type p53-specific CD4(+) T-helper cells. Cancer Res 62:6187–6193

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported in part by a grant from the Deutsche Forschungsgemeinschaft (DFG) (KFO183 TP1 to H.E. and M.T.).

Author information

Authors and Affiliations

  1. Department of Hematology, Oncology and Pneumology, Johannes Gutenberg-University Medical Center, Langenbeckstrasse 1, 55131, Mainz, Germany

    Hakim Echchannaoui & Matthias Theobald

Authors
  1. Hakim Echchannaoui
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Matthias Theobald
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Matthias Theobald .

Editor information

Editors and Affiliations

  1. International Prevention Research Instit, 95 cours Lafayette, Lyon, 69006, France

    Pierre Hainaut

  2. International Agency for Cancer Research, 150 Cours Albert-Thomas, Lyon, 69372, France

    Magali Olivier

  3. Cancer Center Karolinska (CCK), Dept. Oncology and Pathology, Karolinska Institute, Karolinska Institutet, Stockholm, 171 76, Sweden

    Klas G. Wiman

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Echchannaoui, H., Theobald, M. (2013). p53 Immunotherapy of Cancer. In: Hainaut, P., Olivier, M., Wiman, K. (eds) p53 in the Clinics. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3676-8_15

Download citation

Publish with us

Policies and ethics

Search

Navigation