Whole-cell cancer vaccine
Whole cell vaccine is a form of Immunotherapy which uses whole tumor cells from patient, which acts as a source of antigen. The cells are reprogrammed in laboratory conditions to alter the cancerous properties and then re-implanted in patient's body. The cells then stimulate the immune system to act against the tumor cells and clear them out, thus it is a form of Therapeutic vaccine..[1]. In addition to whole cell vaccine, tumor shed antigen and tumor cell lysate vaccines are also used. The rationale behind using whole cell vaccine is that cell provides a source of all antigen at once thus eliminating the need to purify a specific antigen to be used against cancer. The single antigen target approach, in which a single tumor antigen/ epitope which is uniquely expressed or over-expressed in cancerous tissue is targeted has limitations due to the chosen antigen and Major histocompatibility complex (MHC) of patient. Moreover, multiple tumor antigens can be targeted at the same time which generates immune response to more than one tumor related antigens.[2]. On the other hand, other cancer treatment modalities, such as Radiation therapy, Chemotherapy or surgical procedure have associated side-effects as well as decreases the quality of life for patients. Thus whole cell based cancer immunotherapy which is polyvalent holds a great promise to generate lasting protective immune response and avoid tumor recurrence. Whole cell cancer vaccine is in current development and clinical trials to help treat Cancer.
History and Development[edit]
One of the earliest attempts to develop cell-based cancer vaccines was by William Coley, a New York surgeon, first noted that getting an infection after surgery seemed to help some cancer patients. He injected the inactivated Streptococcus pyogenes and Serratia marcescens into the tumor of patients. Later on, remission of tumor was observed. In the late 1800s, he began treating cancer patients by infecting them with certain kinds of bacteria, which came to be known as "coley toxins" [3]. Hanna and Peters used patient derived tumor cells, irradiated them and combined them with an adjuvant (BCG) in laboratory. They then re-injected the tumor cells into the patients from whom the cells were isolated[4]. This was the first time whole cell cancer vaccines were tested. Cancer cell vaccines have been tested in various cancers including colorectal cancer, lung cancer, renal cell cancer, melanoma and prostrate cancer. Myriad whole cell cancer vaccines have successfully passed phase I and phase II clinical trials. However, their clinical transfer has been in-efficacious and challenging during phase III. The whole cell cancer vaccines are still in their developmental stages with one whole-cell based cancer vaccine Sipuleucel-T approved by FDA in 2014 for prostrate cancer [5].
Strategies to develop whole cell vaccines[edit]
Source of Antigen[edit]
The tumor antigen can be isolated from the patient itself (Autologous) or derived from pre-existing tumor cell lines (Allogeneic). The tumor cell can be used as a whole or the antigens shed in culture supernatent can also be used. Both sources of antigens gives a diverse range of potential epitopes to present to patient's system. This ensures that the immune system recognizes the antigen and antigen loss is prevented, as antigen loss has been reported in case of peptide-based immunotherapy [6].
Autologous Whole Cell Vaccine[edit]
Autologous whole cell vaccine is derived from the patient himself. It is important to use patient's own cell or antigens in order for a cancer vaccine to be effective. Autologous whole cell vaccine ensures HLA-type matching and reduces immune rejection [7].
Allogenic Whole cell vaccine[edit]
Allogeneic whole-cell tumor vaccines are derived from the cancer cell lines maintained under laboratory conditions or from another individual. Allogenic whole cell vaccine generates similar kind of antigens as autologous whole cells but they do not have compatibility with patient's HLA. The allogeneic cell lines may be selected for high levels of tumor antigen expression and combined so that at least a partial HLA match is present for most of the potential patient population. Production of allogenic vaccines is more easy as new vaccine is not produced individually for each patient and vaccine is immediately available for use. Moreover, the allogenic vaccines are produced in cell cultures, the sterility of cells is maintained easily for a longer period of time compared to surgical specimen [8]. They are easy to manipulate, produce vaccine at large scale and cost-effective[9].
Tumor Cell Lysate and Tumor shed antigen[edit]
Another source of tumor antigens is lysate of whole cancer cells may also be used. Cell lysate offers advantages over whole cell in two ways. Firstly, since the cellular material is nonviable after cell lysis, replication incompetence is there. Secondly, live cell vaccines require significant amount of time and money to maintain their viability through cryopreservation, this is not the case with tumor cell lysate vaccine which can be stored through lyophilization [10].
Lysate antigens may be taken up by APC and are classically presented to CD4+ T cells in the context of major histocompatibility complex (MHC) class II. In order for these antigens to be presented to CD8+ T cells, they must be processed through a non-classical path known as cross-presentation. Cells used for lysis can be obtained either from autologous tumor cells or from established cells lines [11].
Whole Tumor Cells and Immune Response[edit]
There are two mechanisms by which an immune response is generated against whole cell vaccine. First mechanism states that tumor cell presents antigen directly to the Major Histocompatibility Complex (MCH) via endogenous pathway leading to naive T-cell interaction. While second mechanism is that tumor antigens are picked up and presented to the immune system by dendritic cells, this is called as cross-priming. There are evidences that both mechanism work depending on tumor background. The principle of cross-priming of tumor antigens by dendritic cells is supported by the greater requirement for a match between host MHC and antigen presenting cell (APC) than between host and tumor. It is known that antigen presenting cells capture and present antigen to CD8+ T cells and that this is mediated by dendritic cells [12].
Modified Whole Cell Vaccines[edit]
Tumor cells are poorly immunogenic due to heterologous expression of MHC and co-stimulatory molecules. In order to make whole tumor cell vaccines effective they are modified in several ways.
Transduction of MHC or Co-stimulatory molecules[edit]
In order to efficiently generate anti-cancer immune response, tumor cells have been modified to express co-stimulatory such as CD-86 or CD-80. Preclinical studies in animal models demonstrate that CD80-transfected tumor cells can elicit Cytotoxic T-Lymphocytes (CTL) responses and can protect against tumor challenge in curative models[13]. Wang et al. demonstrated that CD80-transfected autologous tumor cells induced proliferative responses by Periheral Blood Mononuclear Cells (PBMCs) and resulted in a cytolytic response that could kill the parental (untransfected) tumor cell line [14].
Expression of cytokines[edit]
Cytokines are cell signalling molecules which are involved in cell to cell communication between immune cells[15]. A number of cytokines when systematically administered results in immunomodulation of response. For example, Interferon-and interleukin-2 increase or modify vaccine responses, whereas IFN-gamma is known to stimulate up regulation of MHC class I and II and activates T cells, NK cells, and macrophages [16][17]
Adjuvants[edit]
Enhancing immunogenicity of the tumor may not however be enough to break self tolerance, and strong adjuvants are needed to potentiate anti tumor vaccine effects. An adjuvant is a substance that enhances immune response to a vaccine[18]. There are different class of molecules which acts as adjuvants, which include Toll-like receptor (TLR) agonists, cytokines, non-specific immunomodulators, such as Montanide or immunostimulatory antibodies[19]
Genetic modification of Whole Tumor Cells[edit]
Genetic modifications of Whole Tumor Cells can be done by changing cell surface molecules, chemokine, antigens, co-stimulatory molecules, cytokines or the environment in which cancer cells interact with immune system. Tumor cells may be transduced with genes encoding various immunostimulatory cytokines. The addition of granulocyte-macrophage colony stimulating factor (GM-CSF) to a whole tumor cell vaccine resulted in a massive influx of dendritic cells, eosinophils, macrophages and T cells at the site of vaccination. Many phase-I clinical studies have revealed the safety of this approach[20]
References[edit]
- ↑ Razi, Sepideh; Keshavarz-Fathi, Mahsa (2019), "Whole Tumor Cell Vaccine for Cancer", Vaccines for Cancer Immunotherapy, Elsevier, pp. 91–99, doi:10.1016/b978-0-12-814039-0.00007-2, ISBN 9780128140390
- ↑ Keenan, Bridget P.; Jaffee, Elizabeth M. (June 2012). "Whole Cell Vaccines—Past Progress and Future Strategies". Seminars in Oncology. 39 (3): 276–286. doi:10.1053/j.seminoncol.2012.02.007. ISSN 0093-7754. PMC 3356993. PMID 22595050.
- ↑ COLEY, WILLIAM B. (September 1896). "The Therapeutic Value of the Mixed Toxins of the Streptococcus of Erysipelas and Bacillus Prodigiosus in the Treatement of Inoper- Able Malignant Tumors". The American Journal of the Medical Sciences. 112 (3): 251–280. doi:10.1097/00000441-189609000-00001. ISSN 0002-9629.
- ↑ Hanna, M. G.; Peters, L. C. (December 1978). "Specific immunotherapy of established visceral micrometastases by BCG-tumor cell vaccine alone or as an adjunct to surgery". Cancer. 42 (6): 2613–2625. doi:10.1002/1097-0142(197812)42:6<2613::aid-cncr2820420617>3.0.co;2-k. ISSN 0008-543X.
- ↑ Cheever, M. A.; Higano, C. S. (2011-04-06). "PROVENGE (Sipuleucel-T) in Prostate Cancer: The First FDA-Approved Therapeutic Cancer Vaccine". Clinical Cancer Research. 17 (11): 3520–3526. doi:10.1158/1078-0432.ccr-10-3126. ISSN 1078-0432. PMID 21471425.
- ↑ Riker, Adam; Cormier, Janice; Panelli, Monica; Kammula, Udai; Wang, Ena; Abati, Andrea; Fetsch, Patricia; Lee, Kang-Hun; Steinberg, Seth; Rosenberg, Steven; Marincola, Francesco (August 1999). "Immune selection after antigen-specific immunotherapy of melanoma". Surgery. 126 (2): 112–120. doi:10.1016/s0039-6060(99)70143-1. ISSN 0039-6060.
- ↑ Berd, David (March 2002). "M-Vax: an autologous, hapten-modified vaccine for human cancer". Expert Opinion on Biological Therapy. 2 (3): 335–342. doi:10.1517/14712598.2.3.335. ISSN 1471-2598. PMID 11890872.
- ↑ de Gruijl, Tanja D.; van den Eertwegh, Alfons J. M.; Pinedo, Herbert M.; Scheper, Rik J. (2008-06-04). "Whole-cell cancer vaccination: from autologous to allogeneic tumor- and dendritic cell-based vaccines". Cancer Immunology, Immunotherapy. 57 (10): 1569–1577. doi:10.1007/s00262-008-0536-z. ISSN 0340-7004. PMID 18523771.
- ↑ Lattanzi, Maria; Rappuoli, Rino (2005-01-28), "Vaccination: Past, Present and Future", Genomics, Proteomics and Vaccines, John Wiley & Sons, Ltd, pp. 1–22, doi:10.1002/0470012536.ch1, ISBN 978-0-470-01253-6
- ↑ Manmohan Singh, 1964 November 8- editor. Salnikova, Maya, editor. (2015-01-19). Novel approaches and strategies for biologics, vaccines, and cancer therapies. ISBN 978-0-12-416603-5. OCLC 907021491.CS1 maint: Multiple names: authors list (link) CS1 maint: Extra text: authors list (link) Search this book on
- ↑ Faries, Mark B.; Morton, Donald L. (2007), "Whole Cell Vaccines", General Principles of Tumor Immunotherapy, Springer Netherlands, pp. 275–295, doi:10.1007/978-1-4020-6087-8_12, ISBN 9781402060861
- ↑ Nouri-Shirazi, Mahyar; Banchereau, Jacques; Bell, Diana; Burkeholder, Susan; Kraus, Elizabeth T.; Davoust, Jean; Palucka, Karolina A. (2000-10-01). "Dendritic Cells Capture Killed Tumor Cells and Present Their Antigens to Elicit Tumor-Specific Immune Responses". The Journal of Immunology. 165 (7): 3797–3803. doi:10.4049/jimmunol.165.7.3797. ISSN 0022-1767. PMID 11034385.
- ↑ Razi, Sepideh; Keshavarz-Fathi, Mahsa (2019), "Whole Tumor Cell Vaccine for Cancer", Vaccines for Cancer Immunotherapy, Elsevier, pp. 91–99, doi:10.1016/b978-0-12-814039-0.00007-2, ISBN 978-0-12-814039-0
- ↑ Schendel, DJ; Frankenberger, B; Jantzer, P; Cayeux, S; Nöβner, E; Willimsky, G; Maget, B; Pohla, H; Blankenstein, T (December 2000). "Expression of B7.1 (CD80) in a renal cell carcinoma line allows expansion of tumor-associated cytotoxic T lymphocytes in the presence of an alloresponse". Gene Therapy. 7 (23): 2007–2014. doi:10.1038/sj.gt.3301349. ISSN 0969-7128. PMID 11175312.
- ↑ "What are Cytokines?". News-Medical.net. 2009-12-11. Retrieved 2019-11-28.
- ↑ Drucker, Beverly J. (November 2005). "Renal cell carcinoma: Current status and future prospects". Cancer Treatment Reviews. 31 (7): 536–545. doi:10.1016/j.ctrv.2005.07.009. ISSN 0305-7372. PMID 16236454.
- ↑ Ikeda, Hiroaki; Old, Lloyd J; Schreiber, Robert D (April 2002). "The roles of IFNγ in protection against tumor development and cancer immunoediting". Cytokine & Growth Factor Reviews. 13 (2): 95–109. doi:10.1016/s1359-6101(01)00038-7. ISSN 1359-6101. PMID 11900986.
- ↑ "What is an Adjuvant? | ProSci Inc". www.prosci-inc.com. Retrieved 2019-11-28.
- ↑ Chiang, Cheryl Lai-Lai; Kandalaft, Lana E.; Coukos, George (2011-05-10). "Adjuvants for Enhancing the Immunogenicity of Whole Tumor Cell Vaccines". International Reviews of Immunology. 30 (2–3): 150–182. doi:10.3109/08830185.2011.572210. ISSN 0883-0185. PMID 21557641.
- ↑ Chiang, Cheryl; Coukos, George; Kandalaft, Lana (2015-04-23). "Whole Tumor Antigen Vaccines: Where Are We?". Vaccines. 3 (2): 344–372. doi:10.3390/vaccines3020344. ISSN 2076-393X. PMID 26343191.
This article "Whole-cell cancer vaccine" is from Wikipedia. The list of its authors can be seen in its historical and/or the page Edithistory:Whole-cell cancer vaccine. Articles copied from Draft Namespace on Wikipedia could be seen on the Draft Namespace of Wikipedia and not main one.
