Vaccination strategies in lymphoproliferative disorders: Failures and successes

Leukemia Research - Tập 39 - Trang 1006-1019 - 2015
A. Allegra1, S. Russo1, D. Gerace1, L. Calabrò1, V. Maisano1, V. Innao1, C. Musolino1
1Division of Hematology, Department of General Surgery, Oncology and Pathological Anatomy, University of Messina, Messina, Italy

Tài liệu tham khảo

Palomba, 2012, Active immunotherapy: current state of the art in vaccine approaches for NHL, Curr. Oncol. Rep., 14, 433, 10.1007/s11912-012-0255-7 Poppema, 1994, Absence of HLA class I expression by Reed-Sternberg cells, Am. J. Pathol., 145, 37 Drénou, 2002, Major histocompatibility complex abnormalities in non-Hodgkin lymphomas, Br. J. Haematol., 119, 417, 10.1046/j.1365-2141.2002.03814.x Cheson, 2008, Monoclonal antibody therapy for B-cell non-Hodgkin’s lymphoma, N. Engl. J. Med., 359, 613, 10.1056/NEJMra0708875 Janeway, 1975, Recognition of immunoglobulin idiotypes by thymus-derived lymphocytes, Proc. Natl. Acad. Sci. U. S. A., 72, 2357, 10.1073/pnas.72.6.2357 Stevenson, 1990, Anti-idiotypic therapy of leukemias and lymphomas, Chem. Immunol., 48, 126 Levy, 1990, Therapy of lymphoma directed at idiotypes, J. Natl. Cancer Inst. Monogr., 10, 61 Armstrong, 2002, Immunization with a recombinant adenovirus encoding a lymphoma idiotype: induction of tumor-protective immunity and identification of an idiotype-specific T cell epitope, J. Immunol., 168, 3983, 10.4049/jimmunol.168.8.3983 Levy, 1978, Rescue of immunoglobulin secretion from human neoplastic lymphoid cells by somatic cell hybridization, Proc. Natl. Acad. Sci. U. S. A., 75, 2411, 10.1073/pnas.75.5.2411 Neelson, 2008, Listeriolysin O is an improved protein carrier for lymphoma immunoglobulin idiotype and provides systemic protection against 38C13 lymphoma, Cancer Immunol. Immunother., 57, 493, 10.1007/s00262-007-0388-y Iurescia, 2012, Epitope-driven DNA vaccine design employing immunoinformatics against B-cell lymphoma: a biotech’s challenge, Biotechnol. Adv., 30, 372, 10.1016/j.biotechadv.2011.06.020 Lopez-Requena, 2007, Gangliosides, Ab1 and Ab2 antibodies III. The idiotype of anti-ganglioside mAb P3 is immunogenic in a T cell-dependent manner, Mol. Immunol., 44, 2915, 10.1016/j.molimm.2007.01.010 Li, 1997, Mammalian cell expression of dimeric small immune proteins (SIP), Protein Eng., 10, 731, 10.1093/protein/10.6.731 Benvenuti, 2001, Anti-idiotypic antibodies induced by genetic immunisation are directed exclusively against combined V(L)/V(H) determinants, Gene Ther., 8, 1555, 10.1038/sj.gt.3301546 Benvenuti, 2002, Genetic vaccination for the immunotherapy of B-cell malignancies, Curr. Gene Ther., 2, 235, 10.2174/1566523024605654 Cesco-Gaspere, 2008, Boosting anti-idiotype immune response with recombinant AAV enhances tumour protection induced by gene gun vaccination, Scand. J. Immunol., 68, 58, 10.1111/j.1365-3083.2008.02119.x Dupuis, 2000, Distribution of DNA vaccines determines their immunogenicity after intramuscular injection in mice, J. Immunol., 165, 2850, 10.4049/jimmunol.165.5.2850 Timmerman, 2001, Idiotype-encoding recombinant adenoviruses provide protective immunity against murine B-cell lymphomas, Blood, 97, 1370, 10.1182/blood.V97.5.1370 Chen, 2009, Amplification of immune responses against a DNA-delivered idiotypic lymphoma antigen by fusion to the B subunit of E. coli heat labile toxin, Vaccine, 27, 4289, 10.1016/j.vaccine.2009.05.025 Syrengelas, 1996, DNA immunization induces protective immunity against B-cell lymphoma, Nat. Med., 2, 1038, 10.1038/nm0996-1038 Inoges, 2011, Idiotype vaccines for lymphoma: potential factors predicting the induction of immune responses, Word J. Clin. Oncol., 2, 237, 10.5306/wjco.v2.i6.237 Inoges, 2009, Prolonged idiotypic vaccination against follicular lymphoma, Leuk. Lymphoma, 50, 47, 10.1080/10428190802601122 Davis, 1998, Anti-idiotype antibodies can induce long-term complete remissions in non-Hodgkin’s lymphoma without eradicating the malignant clone, Blood, 92, 1184, 10.1182/blood.V92.4.1184 Meeker, 1985, Emergence of idiotype variants during treatment of B-cell lymphoma with anti-idiotype antibodies, N. Engl. J. Med., 312, 1658, 10.1056/NEJM198506273122602 Hollander, 2012, Immunotherapy for B-cell lymphoma: current status and prospective advances, Front. Immunol., 3, 10.3389/fimmu.2012.00003 Lauritzsen, 1994, Naive idiotype-specific CD4+ T cells and immunosurveillance of B-cell tumors, Proc. Natl. Acad. Sci. U. S. A., 91, 5700, 10.1073/pnas.91.12.5700 Strothmeyer, 2010, Comparative analysis of predicted HLA binding of immunoglobulin idiotype sequences indicates T cell-mediated immunosurveillance in follicular lymphoma, Blood, 116, 1734, 10.1182/blood-2010-02-270199 Coelho, 2010, Glycosylation of surface Ig creates a functional bridge between human follicular lymphoma and microenvironmental lectins, Proc. Natl. Acad. Sci. U. S. A., 107, 18587, 10.1073/pnas.1009388107 Zhu, 2002, Acquisition of potential N-glycosylation sites in the immunoglobulin variable region by somatic mutation is a distinctive feature of follicular lymphoma, Blood, 99, 2562, 10.1182/blood.V99.7.2562 Radcliffe, 2007, Human follicular lymphoma cells contain oligomannose glycans in the antigen-binding site of the B-cell receptor, J. Biol. Chem., 282, 7405, 10.1074/jbc.M602690200 Zabalegui, 2004, Acquired potential N-glycosylation sites within the tumor-specific immunoglobulin heavy chains of B-cell malignancies, Haematologica, 89, 541 López-Requena, 2012, Idiotypes as immunogens: facing the challenge of inducing strong therapeutic immune responses against the variable region of immunoglobulins, Front. Oncol., 11 Gocke, 1999, Complete molecular remissions induced by patient-specific vaccination plus granulocyte-monocyte colony-stimulating factor against lymphoma, Nat. Med., 11, 1171 Czerwinski, 2004, Clinical outcome of lymphoma patients after idiotype vaccination is correlated with humoral immune response and immunoglobulin G Fc receptor genotype, J. Clin. Oncol., 11, 4717 Abdalla, 2007, Long-term idiotype vaccination combined with interleukin-12 (IL-12), or IL-12 and granulocyte macrophage colony-stimulating factor, in early-stage multiple myeloma patients, Clin. Cancer Res., 11, 1503 Celsing, 1992, Extramedullary progression of multiple myeloma following GM-CSF treatment–grounds for caution?, Eur J Haematol., 11, 108 Ng, 2012, A vaccine directed to B cells and produced by cell-free protein synthesis generates potent antilymphoma immunity, Proc. Natl. Acad. Sci. U. S. A., 109, 14526, 10.1073/pnas.1211018109 Bettua, 2011, Vaccination with filamentous bacteriophages targeting DEC-205 induces DC maturation and potent anti-tumor T-cell responses in the absence of adjuvants, Eur. J. Immunol., 11, 2573 van, 2010, Engineering filamentous phage carriers to improve focusing of antibody responses against peptides, Vaccine, 11, 2174 Roehnisch, 2013, Chemically linked phage idiotype vaccination in the murine B cell lymphoma 1 model, J. Transl. Med., 11, 267, 10.1186/1479-5876-11-267 Dorostkar, 2012, An endogenous immune adjuvant released by necrotic cells for enhancement of DNA vaccine potency, Iran. J. Immunol., 9, 215 Wang, 1998, Cell immunity against poorly immunogenic tumors by immunization with dendritic cell-tumor fusion vaccines, J. Immunol., 161, 5516, 10.4049/jimmunol.161.10.5516 Ni, 2008, Induction of T-responses against cutaneous T-cell lymphomas ex vivo by autologous dendritic s transfected with amplified tumor mRNA, J. Invest. Dermatol., 128, 2631, 10.1038/jid.2008.125 Van, 2002, Efficient genetic modification of murine dendritic cells by electroporation with mRNA, Cancer Gene Ther., 9, 787, 10.1038/sj.cgt.7700499 Hsu, 2001, clinical trial of sequential dendritic cell, and protein/adjuvant idiotype vaccines in patients with follicular lymphomas, Blood, 98, 466 Saha, 2010, Dendritic cells pulsed with an anti-idiotype antibody mimicking Her-2/neu induced protective antitumor immunity in two lines of Her-2/neu transgenic mice, Cell Immunol., 263, 9, 10.1016/j.cellimm.2010.02.010 Gallagher, 1997, CD40 is expressed on epithelial ovarian cancer cells and modulates growth, Proc. Am. Assoc. Cancer Res., 38, 500 Kluth, 1997, Endothelial expression of CD40 in renal cell carcinoma, Cancer Res., 57, 891 Posner, 1999, Surface membrane-expressed CD40 is present on tumor cells from squamous cell cancer of the head and neck in vitro and in vivo and regulates cell growth in tumor cell lines, Clin. Cancer Res., 5, 2261 Gordon, 2000, Fortifying B cells with CD154, an engaging tale of many hues, Immunology, 100, 269, 10.1046/j.1365-2567.2000.00074.x van, 1997, Functions of CD40 on B cells, dendritic cells and other cells, Curr. Opin. Immunol., 9, 330, 10.1016/S0952-7915(97)80078-7 Ridge, 1998, A conditioned dendritic cell can be a temporal bridge between a CD4+ T helper and a T killer cell, Nature, 393, 474, 10.1038/30989 Bennett, 1998, Help for cytotoxic T-cell responses is mediated by CD40 signalling, Nature, 393, 478, 10.1038/30996 Schoenberger, 1998, T-cell help for cytotoxic T lymphocytes is mediated by CD40-CD40L interactions, Nature, 393, 480, 10.1038/31002 Barr, 2003, A potent adjuvant effect of CD40 antibody attached to antigen, Immunology, 109, 87, 10.1046/j.1365-2567.2003.01634.x Carlring, 2004, CD40 antibody as an adjuvant induces enhanced T cell responses, Vaccine, 22, 3323, 10.1016/j.vaccine.2004.02.043 Carlring, 2012, Conjugation of lymphoma idiotype to CD40 antibody enhances lymphoma vaccine immunogenicity and antitumor effects in mice, Blood, 119, 2956, 10.1182/blood-2011-05-355461 Huang, 2004, Improved immunogenicity of a self tumor antigen by covalent linkage to CD40 ligand, Int. J. Cancer, 108, 696, 10.1002/ijc.11612 Fredriksen, 2007, Chemokine-idiotype fusion DNA vaccines are potentiated by bivalency and xenogeneic sequences, Blood, 110, 1797, 10.1182/blood-2006-06-032938 Timmerman, 2002, Idiotype-pulsed dendritic cell vaccination for B-cell lymphoma: clinical and immune responses in 35 patients, Blood, 99, 1517, 10.1182/blood.V99.5.1517 Di Nicola, 2009, Vaccination with autologous tumor-loaded dendritic cells induces clinical and immunologic responses in indolent B-cell lymphoma patients with relapsed and measurable disease: a pilot study, Blood, 113, 18, 10.1182/blood-2008-06-165654 Manzur, 2012, Enhanced therapeutic effect of B cell-depleting anti-CD20 antibodies upon combination with in-situ dendritic cell vaccination in advanced lymphoma, Clin. Exp. Immunol., 170, 291, 10.1111/j.1365-2249.2012.04658.x Franki, 2008, Dendritic cells loaded with apoptotic antibody-coated tumor cells provide protective immunity against B-cell lymphoma in vivo, Blood, 111, 1504, 10.1182/blood-2007-03-080507 Dhodapkar, 2002, Antitumor monoclonal antibodies enhance cross-presentation of ular antigens and the generation of myeloma-specific killer T s by dendritic cells, J. Exp. Med., 195, 125, 10.1084/jem.20011097 Selenco, 2001, CD20 antibody (C2B8)-induced apoptosis of lymphoma cells promotes phagocytosis by dendritic cells and cross-priming of CD8+ cytotoxic T cells, Leukemia, 15, 1619, 10.1038/sj.leu.2402226 Abes, 2010, Long-lasting anti-tumor protection by anti-CD20 antibody through cellular immune response, Blood, 116, 926, 10.1182/blood-2009-10-248609 Cartron, 2004, From the bench to the bedside: ways to improve rituximab efficacy, Blood, 104, 2635, 10.1182/blood-2004-03-1110 Warncke, 2011, Control of the specificity of T cell-mediated anti-idiotype immunity by natural regulatory T cells, Cancer Immunol. Immunother., 60, 49, 10.1007/s00262-010-0918-x Hömberg, 2014, CD40-independent natural killer-cell help promotes dendritic cell vaccine-induced T-cell immunity against endogenous B-cell lymphoma, Int. J. Cancer, 26 Mattarollo, 2012, NKT cell adjuvant-based tumor vaccine for treatment of myconcogene-driven mouse B-cell lymphoma, Blood, 120, 3019, 10.1182/blood-2012-04-426643 Liggins, 2004, Serologic detection of diffuse large B-cell lymphoma-associated antigens, Int. J. Cancer, 110, 563, 10.1002/ijc.20170 Zwick, 2009, Analysis of the antibody repertoire of patients with mantle cell lymphoma directed against mantle cell lymphoma-associated antigens, Ann. Hematol., 88, 999, 10.1007/s00277-009-0711-0 Nishikawa, 2012, Cancer/testis antigens are novel targets of immunotherapy for adult T-cell leukemia/lymphoma, Blood, 119, 3097, 10.1182/blood-2011-09-379982 Inaoka, 2011, An overview of cancer/testis antigens expression in classical Hodgkin’s lymphoma (cHL) identifies MAGE-A family and MAGE-C1 as the most frequently expressed antigens in a set of Brazilian cHL patients, BMC Cancer, 11, 416, 10.1186/1471-2407-11-416 Winkler, 2012, Hodgkin’s lymphoma RNA-transfected dendritic cells induce cancer/testis antigen-specific immune responses, Cancer Immunol. Immunother., 61, 1769, 10.1007/s00262-012-1239-z Palomba, 2005, CD8+ T-cell-dependent immunity following xenogeneic DNA immunization against CD20 in a tumor challenge model of B-cell lymphoma, Clin. Cancer Res., 11, 370, 10.1158/1078-0432.370.11.1 Helm, 2013, Targeting c-MYC with T-Cells, PLoS One, 8, e77375, 10.1371/journal.pone.0077375 Luo, 2009, Principles of cancer therapy: oncogene and non-oncogene addiction, Cell, 136, 823, 10.1016/j.cell.2009.02.024 Khalil, 2011, Heat shock proteins in oncology: diagnostic biomarkers or therapeutic targets?, Biochim. Biophys. Acta, 1816, 89 Zappasodi, 2011, Serological identification of HSP105 as a novel non-Hodgkin lymphoma therapeutic target, Blood, 118, 4421, 10.1182/blood-2011-06-364570 Weng, 2012, TCL1: a shared tumor-associated antigen for immunotherapy against B-cell lymphomas, Blood, 120, 1613, 10.1182/blood-2011-09-382838 Martorelli, 2012, IGKV3 proteins as candidate off-the-shelf vaccines for kappa-light chain-restricted B-cell non-Hodgkin lymphomas, Clin. Cancer Res., 18, 4080, 10.1158/1078-0432.CCR-12-0763 Inoges, 2014, Idiotype vaccine production using hybridoma technology, Methods Mol. Biol., 1139, 367, 10.1007/978-1-4939-0345-0_30 Bendandi, 2006, Clinical benefit of idiotype vaccines: too many trials for a clever demonstration?, Rev. Recent Clin. Trials, 1, 67, 10.2174/157488706775246120 Bendandi, 2009, Idiotype vaccines for lymphoma: proof-of-principles and clinical trial failures, Nat. Rev. Cancer, 9, 675, 10.1038/nrc2717 Inogès, 2006, Clinical benefit associated with idiotypic vaccination in patients with follicular lymphoma, J. Natl. Cancer Inst., 98, 1292, 10.1093/jnci/djj358 Neelapu, 2005, Phase III. Randomized trial of patient-specific vaccination for previously untreated patients with follicular lymphoma in first complete remission: protocol summary and interim report, Clin Lymphoma, 6, 61, 10.3816/CLM.2005.n.031 Freedman, 2009, Placebo-controlled phase III trial of patient-specific immunotherapy with mitumprotimut-T and granulocyte-macrophage colony-stimulating factor after rituximab in patients with follicular lymphoma, J. Clin. Oncol., 27, 3036, 10.1200/JCO.2008.19.8903 Schuster, 2011, Vaccination with patient-specific tumor-derived antigen in first remission improves disease-free survival in follicular lymphoma, J. Clin. Oncol., 29, 2787, 10.1200/JCO.2010.33.3005 Levy, 2014, Active idiotypic vaccination versus control immunotherapy for follicular lymphoma, J. Clin. Oncol., 32, 1797, 10.1200/JCO.2012.43.9273 Ai, 2009, Anti-idiotype antibody response after vaccination correlates with overall survival in follicular lymphoma, Blood, 113, 5743, 10.1182/blood-2009-01-201988 Davis, 2001, Idiotype vaccination following ABMT can stimulate specific anti-idiotype immune responses in patients with B-cell lymphoma, Biol. Blood Marrow Transplant., 7, 517, 10.1053/bbmt.2001.v7.pm11669219 Park, 2008, Developing idiotype vaccines for lymphoma: from preclinical studies to phase III clinical trials, Br. J. Haematol., 142, 179, 10.1111/j.1365-2141.2008.07143.x Goldstein, 2011, A CpG-loaded tumor cell vaccine induces antitumor CD4+ T cells that are effective in adoptive therapy for large and established tumors, Blood, 117, 118, 10.1182/blood-2010-06-288456 Zhou, 2008, Immunotherapy in mantle cell lymphoma: anti-CD20-based therapy and beyond, Am. J. Hematol., 83, 144, 10.1002/ajh.21036 Turner, 2003, Vav-promoter regulated oncogenic fusion protein NPM-ALK in transgenic mice causes B-cell lymphomas with hyperactive Jun kinase, Oncogene, 22, 7750, 10.1038/sj.onc.1207048 Chiarle, 2003, NPM-ALK transgenic mice spontaneously develop T-cell lymphomas and plasma cell tumors, Blood, 101, 1919, 10.1182/blood-2002-05-1343 Turner, 2006, CD2 promoter regulated nucleophosmin-anaplastic lymphoma kinase in transgenic mice causes B lymphoid malignancy, Anticancer Res., 26, 3275 Merkel, 2011, Novel therapeutic options in anaplastic large cell lymphoma: molecular targets and immunological tools, Mol. Cancer Ther., 10, 1127, 10.1158/1535-7163.MCT-11-0042 Chiarle, 2008, The anaplastic lymphoma kinase is an effective oncoantigen for lymphoma vaccination, Nat. Med., 14, 676, 10.1038/nm1769 Willemze, 2005, WHO-EORTC classification for cutaneous lymphomas, Blood, 105, 3768, 10.1182/blood-2004-09-3502 Maier, 2003, Vaccination of patients with cutaneous T-cell lymphoma using intranodal injection of autologous tumor-lysate-pulsed dendritic cells, Blood, 102, 2338, 10.1182/blood-2002-08-2455 Geskin, 2010, Patient-specific dendritic cell immunization against tumor in Sezary syndrome, J. Invest. Dermatol., 130, s56 Heinzerling, 2005, Oncolytic measles virus in cutaneous T-cell lymphomas mounts antitumor immune responses in vivo and targets interferon-resistant tumor cells, Blood, 106, 2287, 10.1182/blood-2004-11-4558 Kim, 2012, In situ vaccination against mycosis fungoides by intratumoral injection of a TLR9 agonist combined with radiation: a phase 1/2 study, Blood, 119, 355, 10.1182/blood-2011-05-355222 Nishikawa, 2012, Cancer/testis antigens are novel targets of immunotherapy for adult T-cell leukemia/lymphoma, Blood, 119, 3097, 10.1182/blood-2011-09-379982 Ansell, 2011, Identifying patients with follicular lymphoma who are likely to benefit from an idiotype vaccine, J. Clin. Oncol., 29, 2748, 10.1200/JCO.2011.35.8812 Schuster, 2011, Idiotype vaccination as consolidation therapy: time for integration into standard of care for follicular lymphoma?, J. Clin. Oncol., 29, 4845, 10.1200/JCO.2011.38.6094 Inoges, 2011, Stem cell transplant and idiotypic vaccination for B-cell malignancies, Curr. Top. Med. Chem., 11, 1653, 10.2174/156802611796117676 Higano, 2008, Phase 1/2 dose-escalation study of a GM-CSF-secreting, allogeneic, cellular immunotherapy for metastatic hormone-refractory prostate cancer, Cancer, 113, 975, 10.1002/cncr.23669 Borrello, 2000, Sustaining the graft-versus-tumor effect through posttransplant immunization with granulocyte-macrophage colony-stimulating factor (GM-CSF)-producing tumor vaccines, Blood, 95, 3011, 10.1182/blood.V95.10.3011 Teshima, 2001, Tumor cell vaccine elicits potent antitumor immunity after allogeneic T-cell-depleted bone marrow transplantation, Cancer Res., 61, 162 Ho, 2009, GM-CSF-secreting leukemia cell vaccines early after allogeneic stem cell transplantation, Proc. Natl. Acad. Sci. U. S. A., 106, 15825, 10.1073/pnas.0908358106 Burkhardt, 2013, Autologous CLL cell vaccination early after transplant induces leukemia-specific T cells, J. Clin. Invest., 123, 3756, 10.1172/JCI69098 Holman, 2012, Idiotype immunization following high-dose therapy and autologous stem cell transplantation for non-Hodgkin lymphoma, Biol. Blood Marrow Transplant., 18, 257, 10.1016/j.bbmt.2011.06.011 Sow, 2013, Combining low-dose or metronomic chemotherapy with anticancer vaccines. A therapeutic opportunity for lymphomas, Oncoimmunology, 2, e27058 Liu, 2010, Pre-treatment with chemotherapy can enhance the antigenicity and immunogenicity of tumours by promoting adaptive immune responses, Br. J. Cancer, 102, 115, 10.1038/sj.bjc.6605465 Schiavoni, 2011, Cyclophosphamide synergizes with type I interferons through systemic dendritic cell reactivation and induction of immunogenic tumor apoptosis, Cancer Res., 71, 768, 10.1158/0008-5472.CAN-10-2788 Redfern, 2006, Phase II. Clinical trial of idiotype vaccination in previously treated patients with indolent non-Hodgkin’s lymphoma resulting in durable clinical responses, J. Clin. Oncol., 24, 3107, 10.1200/JCO.2005.04.4289 Neelapu, 2005, Vaccine induced tumor-specific immunity despite severe B-cell depletion in mantle cell lymphoma, Nat. Med., 11, 986, 10.1038/nm1290 French, 2007, Eradication of lymphoma by CD8 T cells following anti-CD40 monoclonal antibody therapy is critically dependent on CD27 costimulation, Blood, 109, 4810, 10.1182/blood-2006-11-057216 Houot, 2009, T-cell modulation combined with intratumoral CpG cures lymphoma in a mouse model without the need for chemotherapy, Blood, 113, 3546, 10.1182/blood-2008-07-170274 Met, 2006, The effect of a therapeutic dendritic cell-based cancer vaccination depends on the blockage of CTLA-4 signaling, Cancer Lett., 231, 247, 10.1016/j.canlet.2005.02.005 Curran, 2011, Combination CTLA-4 blockade and 4-1BB activation enhances tumor rejection by increasing T-cell infiltration, proliferation, and cytokine production, PLoS One, 6, e19499, 10.1371/journal.pone.0019499 Hirschhorn-Cymerman, 2009, OX40 engagement and chemotherapy combination provides potent antitumor immunity with concomitant regulatory T cell apoptosis, J. Exp. Med., 206, 1103, 10.1084/jem.20082205 Jeanbart, 2014, Enhancing efficacy of anticancer vaccines by targeted delivery to tumor-draining lymph nodes, Cancer Immunol. Res., 2, 436, 10.1158/2326-6066.CIR-14-0019-T Grille, 2013, A therapeutic vaccine using Salmonella-modified tumor s combined with interleukin-2 induces enhanced antitumor immunity in B-cell lymphoma, Leuk. Res., 37, 341, 10.1016/j.leukres.2012.10.003 Singh, 2011, An injectable synthetic immune-priming center mediates efficient T- class switching and T-helper 1 response against B cell lymphoma, J Control. Release, 155, 184, 10.1016/j.jconrel.2011.06.008 Peggs, 2008, Cell intrinsic mechanisms of T-cell inhibition and application to cancer therapy, Immunol. Rev., 224, 141, 10.1111/j.1600-065X.2008.00649.x O’Mahony, 2007, A pilot study of CTLA-4 blockade after cancer vaccine failure in patients with advanced malignancy, Clin. Cancer Res., 13, 958, 10.1158/1078-0432.CCR-06-1974 Ansell, 2009, study of ipilimumab, an anti-CTLA-4 monoclonal antibody, in patients with relapsed and refractory B-cell non-Hodgkin lymphoma, Clin. Cancer Res., 15, 6446, 10.1158/1078-0432.CCR-09-1339 Berger, 2008, Phase I. Safety and pharmacokinetic study of CT-011, a humanized antibody interacting with PD-1, in patients with advanced hematologic malignancies, Clin. Cancer Res., 14, 3044, 10.1158/1078-0432.CCR-07-4079 Westin, 2010, University of Texas M. D. Anderson Cancer Center, Houston, TX; CureTech, Yavne, Israel Phase II safety and efficacy study of CT-011, a humanized anti-PD-1 monoclonal antibody, in combination with rituximab in patients with relapsed follicular lymphoma, J. Clin. Oncol., 28 Brahmer, 2008, Lowy safety and activity of MDX-1106 (ONO-4538), an anti-PD-1 monoclonal antibody, in patients with selected refractory or relapsed malignancies, J. Clin. Oncol., 28, 3006, 10.1200/jco.2008.26.15_suppl.3006 Patel, 2011, Escherichia coli-based production of a tumor idiotype antibody fragment—tetanus toxin fragment C fusion protein vaccine for B cell lymphoma, Protein Expr. Purif., 2011, 15, 10.1016/j.pep.2010.09.005 Betting, 2009, Enhanced immune stimulation by a therapeutic lymphoma tumor antigen vaccine produced in insect cells involves mannose receptor targeting to antigen presenting cells, Vaccine, 27, 250, 10.1016/j.vaccine.2008.10.055 Neelapu, 2004, Human autologous tumor-specific T-cell responses induced by liposomal delivery of a lymphoma antigen, Clin. Cancer Res., 10, 8309, 10.1158/1078-0432.CCR-04-1071 Park, 2013, is a Toll-like receptor 4 agonist that inhibits tumor growth by activating dendritic cell-mediated CD8+ T cells, Exp. Mol. Med., 45, 8, 10.1038/emm.2013.14 Liu, 2011, Vaccination with immunoglobulin frame region-derived nonapeptide elicits cellular immune response againstlymphoma in human leukocyte antigen-A2.1 transgenic mice, Leuk. Lymphoma, 52, 1795, 10.3109/10428194.2011.577257 Schlapbach, 2011, Telomerase-specific GV1001 peptide vaccination fails to induce objective tumor response in patients with cutaneous T cell lymphoma, J. Dermatol. Sci., 62, 75, 10.1016/j.jdermsci.2011.02.001 Finn, 2008, Cancer immunology, N. Engl. J. Med., 358, 2704, 10.1056/NEJMra072739 Musolino, 2014, Allergy and risk of hematologic malignancies: associations and mechanisms, Leuk. Res., 38, 1137, 10.1016/j.leukres.2014.08.004 Gangemi, 2015, Lymphoproliferative disease and cancer among patients with common variable immunodeficiency, Leuk. Res., 39, 389, 10.1016/j.leukres.2015.02.002 Allegra, 2015, Vaccination of multiple myeloma: current strategies and future prospects, Crit. Rev. Oncol. Hematol., S1040–8428, 121 Gajewski, 2012, Cancer immunotherapy, Mol. Oncol., 6, 242, 10.1016/j.molonc.2012.01.002 Mellman, 2011, Cancer immunotherapy comes of age, Nature, 480, 480, 10.1038/nature10673 Sharma, 2011, Novel cancer immunotherapy agents with survival benefit: recent successes and next steps, Nat. Rev. Cancer, 11, 1, 10.1038/nrc3153 Topalian, 2012, Safety, activity, and immune correlates of anti-PD-1 antibody in cancer, N. Engl. J. Med., 366, 2443, 10.1056/NEJMoa1200690 Cochran, 2006, Tumour-induced immune modulation of sentinel lymph nodes, Nat. Rev. Immunol., 6, 659, 10.1038/nri1919 Navarrete, 2011, Upfront immunization with autologous recombinant idiotype Fab fragment without prior cytoreduction in indolent B-cell lymphoma, Blood, 117, 1483, 10.1182/blood-2010-06-292342 Sakamaki, 2011, Translational development of vaccination strategies in follicular NHL, Best Pract. Res. Clin. Haematol., 24, 295, 10.1016/j.beha.2011.03.007 Muraro, 2013, Successes, failures and new perspectives of idiotypic vaccination for B-cell non-Hodgkin lymphomas, Hum. Vaccin. Immunother., 9, 1078, 10.4161/hv.23970