Theme 4: Vaccines
Overview: Several CCIR members are developing therapeutic vaccines for different types of cancer and finding ways to improve their efficacy. The ability to generate a strong immune response in vivo through vaccination is critical to the successful induction of immunity against infectious agents and cancer. Three randomized clinical trials have recently demonstrated the benefits of vaccination for patients with melanoma, lymphoma and prostate cancer. Drs. Hwu and Kwak were leaders in two of these pivotal trials (Schwartzentruber DJ, N Engl Med. 2011; Schuster SJ, J Clin Oncol. 2011). In addition, the availability of agents that are capable of enhancing immune responses, such as TLR agonists, cytokines, and immunomodulatory antibodies, underscores the importance of developing rational combinations of agents to optimally activate cellular and humoral immunity against pathogens and cancer.
Some highlights from Fiscal Year 2013 include:
• A recent study demonstrated that lenalidomide, in addition to its own cytotoxic effects on tumor cells, can also serve as an immune adjuvant in combination with vaccine therapy, as demonstrated in tumor-bearing mice, via two proposed mechanisms: effect on T-cell activation to boost adaptive antitumor immunity and amelioration of tumor-induced immune suppression (Sakamaki I, Leukemia, 2013)
• Vaccination with Dickkopf-1 (DKK1), broadly expressed in myeloma cells but highly restricted in normal tissues, was shown to protect mice from developing myeloma and also shown to be therapeutic against established myeloma, thus providing strong and direct evidence to support the application of DKK1-based immunotherapy in myeloma patients (Qian J, Blood, 2012)
• A study recently published in Nature Medicine demonstrated that peptide/IFA-based vaccination sites may outcompete tumor sites for T cell recognition, chemokine production, T cell accumulation and tissue destruction; these findings may help explain the typically limited clinical benefit of antigen-specific CD8+ T cells induced by a widely used class of cancer vaccines (Hailemichael Y, Nat Med. 2013)
• The Annual Texas Cancer Vaccine Symposium was organized and sponsored by the CCIR, held in the S. Campus Research Building at MD Anderson Cancer Center on January 13, 2014. Over 100 participants attended the Symposium, representing more than 10 different institutions throughout the state of Texas. The Symposium included 14 oral presentations as well as a poster session, forming the basis for many new collaborations and grant opportunities.
Additional Relevant Publications:
- Chung Y, Lee YH, Zhang Y, Martin-Orozco N, Yamazaki T, Zhou D, Kang CY, Hwu P, Kwak LW, Dong C. T cells and T cell tumors efficiently generate antigen-specific cytotoxic T cell immunity when modified with an NKT ligand. Oncoimmunology. 2012, 1(2):141-151.
- Weng J, Rawal S, Chu F, Park HJ, Sharma R, Delgado DA, Fayad L, Fanale M, Romaguera J, Luong A, Kwak LW, Neelapu SS. TCL1: a shared tumor-associated antigen for immunotherapy against B-cell lymphomas. Blood. 2012, 120(8):1613-23.
- Hong S, Qian J, Li H, Yang J, Lu Y, Zheng Y, Yi Q. CpG or IFN-α are more potent adjuvants than GM-CSF to promote anti-tumor immunity following idiotype vaccine in multiple myeloma. Cancer Immunol Immunother. 2012, 61(4):561-71.
- Rodriguez-Cruz TG, Liu S, Khalili JS, Whittington M, Zhang M, Overwijk W, Lizee G. Natural splice variant of MHC class I cytoplasmic tail enhances dendritic cell-induced CD8+ T cell responses and boosts anti-tumor immunity. PLoS One. 2011; 6(8):e22939.
- Courtney AN, Thapa P, Singh S, Wishahy AM, Zhou D, Sastry J. Intranasal but not intravenous delivery of the adjuvant α-galactosylceramide permits repeated stimulation of natural killer T cells in the lung. Eur J Immunol. 2011, 41(11):3312-22.
- Weng J, Cha SC, Matsueda S, Alatrash G, Popescu MS, Yi Q, Molldrem JJ, Wang M, Neelapu SS, Kwak LW. Targeting human B-cell malignancies through Ig light chain-specific cytotoxic T lymphocytes. Clin Cancer Res. 2011, 17(18):5945-52.
- Singh A, Qin H, Fernandez I, Wei J, Lin J, Kwak LW, Roy K. An injectable synthetic immune-priming center mediates efficient T cell class switching and T-helper 1 response against B cell lymphoma. J Control Release. 2011, 155(2):184-92.
- Lou Y, Liu C, Lizee G, Peng W, Xu C, Ye Y, Rabinovich BA, Hailemichael Y, Gelbard A, Zhou D, Overwijk WW, Hwu P. Antitumor activity mediated by CpG: the route of administration is critical. J Immunother. 2011, 34(3):279-88.
- Qin H, Cha SC, Neelapu SS, Liu C, Wang YH, Wei J, Qin XF, Liu YJ, Kwak LW. Generation of an immune microenvironment as a novel mechanism for myotoxins to potentiate genetic vaccines. Vaccine. 2010, 28(50):7970-8.
- Yi Q, Szmania S, Freeman J, Qian J, Rosen NA, Viswamitra S, Cottler-Fox M, Barlogie B, Tricot G, van Rhee F. Optimizing dendritic cell-based immunotherapy in multiple myeloma: intranodal injections of idiotype-pulsed CD40 ligand-matured vaccines led to induction of type-1 and cytotoxic T cell immune responses in patients. Br J Haematol. 2010, 150(5):554-64.
- Qin H, Nehete PN, He H, Nehete B, Buchl S, Cha SC, Sastry JK, Kwak LW. Prime-boost vaccination using chemokine-fused gp120 DNA and HIV envelope peptides activates both immediate and long-term memory cellular responses in rhesus macaques. J Biomed Biotechnol. 2010, 2010:860160.
- He H, Courtney AN, Wieder E, Sastry KJ. Multicolor flow cytometry analyses of cellular immune response in rhesus macaques. J Vis Exp. 2010, (38).
- Frasca L, Stonier SW, Overwijk WW, Schluns KS. Differential mechanisms of memory CD8 T cell maintenance by individual myeloid cell types. J Leukoc Biol. 2010, 88(1):69-78.
- Weaver EA, Nehete PN, Nehete BP, Buchl SJ, Palmer D, Montefiori DC, Ng P,Sastry KJ, Barry MA. Protection against Mucosal SHIV Challenge by Peptide and Helper-Dependent Adenovirus Vaccines. Viruses. 2009, 1(3):920.
- Qin H, Cha SC, Neelapu SS, Lou Y, Wei J, Liu YJ, Kwak LW. Vaccine site inflammation potentiates idiotype DNA vaccine-induced therapeutic T cell-, and not B cell-, dependent antilymphoma immunity. Blood. 2009, 114(19):4142-9.
- Qian J, Hong S, Wang S, Zhang L, Sun L, Wang M, Yang J, Kwak LW, Hou J, Yi Q. Myeloma cell line-derived, pooled heat shock proteins as a universal vaccine for immunotherapy of multiple myeloma. Blood. 2009, 114(18):3880-9. .
- Sikora AG, Jaffarzad N, Hailemichael Y, Gelbard A, Stonier SW, Schluns KS, Frasca L, Lou Y, Liu C, Andersson HA, Hwu P, Overwijk WW. IFN-alpha enhances peptide vaccine-induced CD8+ T cell numbers, effector function, and antitumor activity. J Immunol. 2009, 182(12):7398-407.
- Weaver EA, Nehete PN, Buchl SS, Senac JS, Palmer D, Ng P, Sastry KJ, Barry MA. Comparison of replication-competent, first generation, and helper-dependent adenoviral vaccines. PLoS One. 2009, 4(3):e5059.
- Courtney AN, Nehete PN, Nehete BP, Thapa P, Zhou D, Sastry KJ. Alpha-galactosylceramide is an effective mucosal adjuvant for repeated intranasal or oral delivery of HIV peptide antigens. Vaccine. 2009, 27(25-26):3335-41.
- Thapa P, Zhang G, Xia C, Gelbard A, Overwijk WW, Liu C, Hwu P, Chang DZ, Courtney A, Sastry JK, Wang PG, Li C, Zhou D. Nanoparticle formulated alpha-galactosylceramide activates NKT cells without inducing anergy. Vaccine. 2009, 27(25-26):3484-8.
- Hong S, Qian J, Yang J, Li H, Kwak LW, Yi Q. Roles of idiotype-specific T cells in myeloma cell growth and survival: Th1 and CTL cells are tumoricidal while Th2 cells promote tumor growth. Cancer Res. 2008, 68(20):8456-64.
- Stonier SW, Ma LJ, Castillo EF, Schluns KS. Dendritic cells drive memory CD8 T cell homeostasis via IL-15 transpresentation. Blood. 2008, 112(12):4546-54.
- Liu C, Lou Y, Lizee G, Qin H, Liu S, Rabinovich B, Kim GJ, Wang YH, Ye Y, Sikora AG, Overwijk WW, Liu YJ, Wang G, Hwu P. Plasmacytoid dendritic cells induce NK cell-dependent, tumor antigen-specific T cell cross-priming and tumor regression in mice. J Clin Invest. 2008, 118(3):1165-75.
- Nehete PN, Nehete BP, Hill L, Manuri PR, Baladandayuthapani V, Feng L, Simmons J, Sastry KJ. Selective induction of cell-mediated immunity and protection of rhesus macaques from chronic SHIV(KU2) infection by prophylactic vaccination with a conserved HIV-1 envelope peptide-cocktail. Virology. 2008, 370(1):130-41.