The Immune Response Corporation

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The Immune Response Corporation (IRC) was a pharmaceutical company that worked in the development of immunotherapeutic products. The firm was founded by Jonas Salk and Kevin Kimberlin when Kimberlin, "asked Salk to become lead scientific advisor for a new biotech company specializing in 'anti-idiotypes,' a novel vaccine technology." [1] Salk called the proposal "liberating." [2]

Contents

Overview

Francis Crick once said about Salk, "Few have made one discovery that has benefited humanity so greatly. Jonas was a man who, right to his last day, was actively in pursuit of another." [3]

The management team included CEO Jim Glavin, former CEO of Genetic Systems (acquired by Bristol Myers), and Chief Scientific Officer Dennis Carlo, a former Vice President of R&D at Hybritech. [4] Joe O'Neill was appointed as CEO in 2005, [5] because of his work as the chief architect of the President's Emergency Plan for AIDS Relief, known as PEPFAR. [6] [7] [8] Corporate partners that supported IRC included Colgate, The Rorer Group, Rhone Poulenc, The Pasteur Institute, Institute Merieux, NovaRx, Agouron Pharmaceuticals, Bayer, and Pfizer. The company's shares were included in a public offering in 1990.

Products

Cancer Immunotherapy

The company's anti-idiotype antibody program had a significant impact on the ultimate acceptance and success of cancer immunotherapy. It was based on research by Belgian biologist, Jacques Urbain, [9] whom Kimberlin retained, and who reported to Jonas Salk. Urbain's idiotypic research showed a "dramatic enhancement of an antiviral immune response by dendritic cells," thus demonstrating the principle of a dendritic cell-enhanced immunity by means of anti-idiotype antibodies. [10] He followed up with an anti-idiotype tumor vaccine against lymphocytes "not normally recognized" by the immune system. [11] The Immune Response Corporation filed a patent on this invention entitled: "Idiotypic Vaccination Against B-Cell Lymphoma" in May 1990. [9] [12] IRC described the vaccination treatment as utilizing antigen-presenting dendritic cells to stimulate responses to tumor antigens. Preclinical studies published in 1994 in the European Journal of Immunology demonstrated that 8 out of 10 of the treated rats survived post-treatment, whereas the 10 control rats died. [13]   Nature Medicine later reported on  an independent group of scientists at Stanford University who published results of a Phase I clinical trial using this technology to treat patients suffering from B-cell lymphoma. [14]

After incubation and pre-clinical validation by IRC, the dendritic cell product was licensed to a startup in exchange for founders stock, $500,000 in cash and royalties. [15] Recognizing the potential for antigen-presenting dendritic cells, that startup changed its name to Dendreon. [16] Its major investor was Paul Allen [17] (Vulcan Ventures owned 22% of the company by the time it went public). Allen had been diagnosed with non-Hodgkin's disease, often a precursor to B-cell lymphoma, the subject of the IRC/Urbain invention. The cell-based immune therapy, based on that invention, Sipuleucel-T, more commonly known as Provenge, became the first FDA-approved immunotherapeutic cancer vaccine. [18] [19]

Sipuleucel-T, initially approved for treating patients with metastatic prostate cancer who have not responded to hormone therapy, [20] was then recommended in 2015 by the National Comprehensive Cancer Network as a first-line treatment for patients with metastatic Castration Resistant Prostate Cancer. [21] According to its manufacturer, the Sanpower Group, more than 40,000 men had been prescribed Sipuleucel-T as of 2017. [22]

After its U.S. market introduction, the process and facility that produced this immunotherapeutic became a key to the approval of Kymriah, the first CAR-T immunotherapy (chimeric antibody receptor T-Cell) to reach the market. [23] Its developer, Novartis, required a complex manufacturing infrastructure capable of delivering an immunotherapeutic of consistent quality in order to produce the clinical and commercial quantities needed to obtain FDA approval. Since the team running the manufacturing facility were experts at producing and distributing the only commercially available cell-based cancer immunotherapy, Novartis bought the rights to the process and the FDA-approved facility and hired the 100 person team making the prostate cancer immunotherapy. [23] [24] On August 13, 2017, Kymriah became the world's first gene therapy to reach the market, [25] an approval that was recognized by FDA Commissioner Scott Gottlieb with these remarks, "Today marks another milestone in the development of a whole new scientific paradigm of the treatment of serious diseases." [26]

HIV Immunotherapeutic

The AIDS immunotherapy sponsored by IRC was based a hypothesis by Jonas Salk, published in Nature, "Prospects for the Control of AIDS through Immunization of Seropositive Individuals." [27]

Designed to help HIV-infected patients mount a more vigorous immune response, it was rooted in the principle of non-infectious viral immunization pioneered by Salk in his influenze and polio vaccines, both standards throughout the world today. Other companies at the time were testing HIV therapies but none "moved more aggressively toward large-scale human trials" according to an article in The New York Times. [28] For example, IRC applied for trial approval, and within 35 days, in November, 1987, sponsored the first HIV vaccine trial on humans "under a 1987 law that allows California researchers to test new AIDS therapies without seeking federal approval." [29] The subsequent Phase III trial, Study 806, was the first-ever large-scale trial to study an immune-based therapy. [30] Enrolling 2,527 patients, it was a random, placebo-controlled trial to assess the HIV immune therapy in combination with antiviral drugs. The end point was slowing the progression to AIDS or death for patients having CD4 T-cells between 300 and 549 cells/mm. [31]

Bruce Walker commented on the outcome of Study 806. Walker was the director of the Harvard Medical School division of AIDS at Massachusetts General Hospital, the largest teaching hospital for Harvard Medical School. He wrote, "The study was stopped prematurely due to the decrease in AIDS-related illness resulting from the introduction of more effective antiviral drug combinations. In addition, the study was not well controlled. Participants differed in terms of the antiviral medications during the course of that study, making interpretation of the findings problematic." The problematic outcome adversely impacted funding, and so, after raising $350 million, the Company abandoned the project and liquidated its assets in 2008.  Nonetheless, Walker recognized this as "the first clear demonstration of the potential reconstitution of the immune response in chronic HIV infection...This is the first proof of the principle that therapeutic vaccination can help people with chronic HIV infection mount a strong CD4 helper cell response." [32]

Related Research Articles

Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as activation immunotherapies, while immunotherapies that reduce or suppress are classified as suppression immunotherapies. Immunotherapy is under preliminary research for its potential to treat various forms of cancer.

A cancer vaccine, or oncovaccine, is a vaccine that either treats existing cancer or prevents development of cancer. Vaccines that treat existing cancer are known as therapeutic cancer vaccines or tumor antigen vaccines. Some of the vaccines are "autologous", being prepared from samples taken from the patient, and are specific to that patient.

This is a list of AIDS-related topics, many of which were originally taken from the public domain U.S. Department of Health Glossary of HIV/AIDS-Related Terms, 4th Edition.

<span class="mw-page-title-main">Cancer immunotherapy</span> Artificial stimulation of the immune system to treat cancer

Cancer immunotherapy (immuno-oncotherapy) is the stimulation of the immune system to treat cancer, improving the immune system's natural ability to fight the disease. It is an application of the fundamental research of cancer immunology (immuno-oncology) and a growing subspecialty of oncology.

Anti-idiotypic vaccines consist of antibodies that have three-dimensional immunogenic regions, termed idiotopes, that consist of protein sequences that bind to cell receptors. Idiotopes are aggregated into idiotypes specific to their target antigen. An example of an anti-idiotype antibody is Racotumomab.

<span class="mw-page-title-main">Abagovomab</span> Chemical compound

Abagovomab is a mouse anti-idiotype monoclonal antibody whose variable epitope mirrors a tumour antigen (CA-125) highly expressed in the epithelial ovarian cancer. Abagovomab does not bind directly to CA-125, but it works as a "surrogate" antigen, enabling the immune system to identify and attack tumour cells displaying the CA-125 protein. Through this, it is hoped that the body's immune system may be able to combat any remaining individual tumour cells and thus prevent recurrence of the disease.

<span class="mw-page-title-main">Ipilimumab</span> Pharmaceutical drug

Ipilimumab, sold under the brand name Yervoy, is a monoclonal antibody medication that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system.

Dendreon is a biotechnology company. Its lead product, Provenge, is an immunotherapy for prostate cancer. It consists of a mixture of the patient's own blood cells that have been incubated with the Dendreon PAP-GM-CSF fusion protein. Phase III clinical trial results demonstrating a survival benefit for prostate cancer patients receiving the drug were presented at the AUA meeting on April 28, 2009. After going through the approval process, Provenge was given full approval by the FDA on April 29, 2010. Dendreon's stock value fell 66% on August 4, 2011, after abandoning its forecast for its debut drug Provenge.

Biovest International, Inc was a Minneapolis-based biotechnology company. Their active immunotherapy, BiovaxID, is a cancer vaccine whose first indication was intended to be consolidation/adjuvant therapy of follicular Non-Hodgkin's Lymphoma. Biovest filed to reorganize under chapter 11 bankruptcy in 2014, BiovaxID was refused European marketing authorization in 2015, and Biovest's stock listing was revoked in 2017.

Active immunotherapy is a type of immunotherapy that aims to stimulate the host's immune system or a specific immune response to a disease or pathogen and is most commonly used in cancer treatments. Active immunotherapy is also used for treatment of neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, prion disease, and multiple sclerosis. Active immunotherapies induce an immune response through direct immune system stimulation, while immunotherapies that administer antibodies directly to the system are classified as passive immunotherapies. Active immunotherapies can elicit generic and specific immune responses depending on the goal of the treatment. The categories of active immunotherapy divide into:

Sipuleucel-T, sold under the brand name Provenge, developed by Dendreon Pharmaceuticals, LLC, is a cell-based cancer immunotherapy for prostate cancer (CaP). It is an autologous cellular immunotherapy.

Neuvenge, Lapuleucel-T, is a therapeutic cancer vaccine (TCV) in development by Dendreon (DNDN). It uses the "immunotherapy platform approach" first successfully demonstrated on the U.S. Food and Drug Administration (FDA)-approved TCV Provenge. It was first tested on breast cancer patients with tumors expressing HER2/neu, and is now scheduled to be tested on bladder cancer patients.

Gustav Gaudernack is a scientist working in the development of cancer vaccines and cancer immunotherapy. He has developed various strategies in immunological treatment of cancer. He is involved in several ongoing cellular and immuno-gene therapeutic clinical trials and his research group has put major efforts into the development of various T cell-based immunotherapeutic strategies.

Racotumomab is a therapeutic cancer vaccine for the treatment of solid tumors that is currently under clinical development by ReComBio, an international public-private consortium with the participation of the Center of Molecular Immunology at Havana, Cuba (CIM) and researchers from Buenos Aires University and National University of Quilmes in Argentina. It induces the patient's immune system to generate a response against a cancer-specific molecular target with the purpose of blocking tumor growth, slowing disease progression and ultimately increasing patient survival.

<span class="mw-page-title-main">Lauren V. Wood</span> American allergist, immunologist

Lauren V. Wood is an American allergist, immunologist, and staff physician at the National Cancer Institute (NCI) at the National Institutes of Health (NIH) in Bethesda, Maryland, where she has served as a principal investigator. She is known for conducting studies of vaccines for cancer, Human papillomavirus (HPV), Hepatitis C, and HIV especially for use with children, teens and young adults. She holds the rank of captain in the U.S. Public Health Service (PHS).

<span class="mw-page-title-main">Cancer Breakthroughs 2020</span>

Cancer Breakthroughs 2020, also known as Cancer Moonshot 2020 is a coalition with the goal of finding vaccine-based immunotherapies against cancer. By pooling the resources of multinational pharmaceutical, biotechnology companies, academic centers and oncologists, it intends to create access to over 60 novel and approved agents under exploration in the war against cancer and is expected to enable rapid testing of novel immunotherapy combination protocols. The initiative is being managed by a consortium of companies called The National Immunotherapy Coalition.

Remune was the first therapeutic HIV vaccine based on the killed whole virus approach. Remune was initially invented by Jonas Salk in 1987 and was developed by Immune Response BioPharma, Inc. (IRBP)

The dendritic cell-based cancer vaccine is an innovation in therapeutic strategy for cancer patients.

Julianna Lisziewicz is a Hungarian immunologist. Lisziewicz headed many research teams that have discovered and produced immunotheraputic drugs to treat diseases like cancer and chronic infections like HIV/AIDS. Some of these drugs have been successfully used in clinical trials.

A therapeutic vaccine is a vaccine which is administered after a disease or infection has already occurred. A therapeutic vaccine works by activating the immune system of a patient to fight an infection. A therapeutic vaccine differs from a prophylactic vaccine in that prophylactic vaccines are administered to individuals as a precautionary measure to avoid the infection or disease while therapeutic vaccines are administered after the individual is already affected by the disease or infection. A therapeutic vaccine fights an existing infection in the body rather than immunizing the body for protection against future diseases and infections. Therapeutic vaccines are mostly used against viral infections. Patients affected with chronic viral infections are administered with therapeutic vaccines, as their immune system is not able to produce enough efficient antibodies.

References

  1. ↑ Nobile, Philip. "Jonas Salk's Quest for an AIDS Vaccine." Village Voice.  October 23, 1990 Vol XXXV No. 43. verification: University of California San Diago Library, https://library.ucsd.edu/speccoll/findingaids/MSS0001_BLR.pdf.%5B%5D
  2. ↑ Charlotte, Jacobs, Jonas Salk : a life, Ward, Pam, ISBN   978-1504663083, OCLC   919967060
  3. ↑ Sherrow, Victoria.  "Jonas Salk, Beyond the Microscope." Revised Edition. Chelsea House Publisher 2008. P 112.
  4. ↑ The Immune Response Corporation, Registration Statement filed with The Securities Exchange Commission. October 28, 1996. Pg 35.
  5. ↑ "Joseph F. O'Neill, M.D., Former Director of the Office of National AIDS Policy, Joins The Immune Response Corporation as CEO and President" . Retrieved 2018-10-08.
  6. ↑ Caryl, Christian (February 14, 2013). "What George W. Bush Did Right". Foreign Policy.
  7. ↑ Plaut, Martin (January 16, 2009). "Has Bush Been Africa's Best Friend?". BBC News.
  8. ↑ "AIDS Battle Burnishes Bush's Legacy in Africa". NBC News. 2009-01-11.
  9. 1 2 WO 1991013632,Bohlen, Heribert; Urbain, Jacques& Thielemans, Kristiaan,"Idiotypic Vaccination Against B Cell Lymphoma",issued 1991/09/20
  10. ↑ Francotte, M.; Urbain, J. (1 December 1985). "Enhancement of antibody response by mouse dendritic cells pulsed with tobacco mosaic virus or with rabbit antiidiotypic antibodies raised against a private rabbit idiotype". Proceedings of the National Academy of Sciences. 82 (23): 8149–8152. Bibcode:1985PNAS...82.8149F. doi: 10.1073/pnas.82.23.8149 . PMC   391460 . PMID   3877936.
  11. ↑ Ellis, Ronald W. "Vaccines: New Approaches to Immunological Problems". Pg 336.
  12. ↑ The Securities and Exchange Commission, Registration Statement for The Immune Response Corporation. 10.28.96. Pgs 29-31. https://www.nasdaq.com/markets/ipos/filing.ashx?filingid=465620
  13. ↑ The Securities and Exchange Commission. Registration Statement for The Immune Response Corporation. 10.28.96. Pg 3029-31.
  14. ↑ Hsu, Frank J.; Benike, Claudia; Fagnoni, Francesco; Liles, Tina Marie; Czerwinski, Debra; Taidi, Behnaz; Engleman, Edgar G.; Levy, Ronald (January 1996). "Vaccination of patients with B–cell lymphoma using autologous antigen–pulsed dendritic cells". Nature Medicine. 2 (1): 52–58. doi: 10.1038/nm0196-52 . PMID   8564842. S2CID   23032398.
  15. ↑ Research, Center for Biologics Evaluation and. "Approved Products - Questions and Answers - Provenge". www.fda.gov. Retrieved 2018-10-18.
  16. ↑ "History". Dendreon.
  17. ↑ "Business | Vulcan Backs Biotech Firm Dendreon With $10 Million | Seattle Times Newspaper". community.seattletimes.nwsource.com. Retrieved 2018-10-18.
  18. ↑ Landau, Elizabeth. "'Landmark' cancer vaccine gets FDA approval". CNN. Retrieved 2018-10-18.
  19. ↑ "Sipuleucel-T". Drugs in R&D. 7 (3): 197–201. 2006. doi:10.2165/00126839-200607030-00006. ISSN   1174-5886. PMID   16752945.
  20. ↑ "Search Detail page". Clinical Trials.
  21. ↑ National Comprehensive Cancer Network . 2016. NCCN Clinical Practice Guidelines in Oncology (NCCN Guideline): Prostate Cancer: Version 1. 2015 November 10. www.nccn.org/professionals/physician_gls/pdf/prostate.pdf.
  22. ↑ "PROVENGE to benefit from State Council meeting decision_Main Articles_News_The Sanpower Group". en.sanpowergroup.com.
  23. 1 2 Herper, Matthew (May 7, 2014). "Is This How We'll Cure Cancer?". Forbes.
  24. ↑ "UPDATED: Novartis buys Dendreon New Jersey plant | FiercePharma". www.fiercepharma.com. Retrieved 2018-10-09.
  25. ↑ Mukherjee, Sy. "The Way We Treat Cancer Will Be Revolutionized As Gene Therapy Comes to the U.S". Fortune Magazine. August 30, 2017.
  26. ↑ "Press Announcements - FDA approves CAR-T cell therapy to treat adults with certain types of large B-cell lymphoma". www.fda.gov. U.S. Food & Drug Administration. October 18, 2017.
  27. ↑ Salk, Jonas (June 1987). "Prospects for the control of AIDS by immunizing seropositive individuals". Nature. 327 (6122): 473–476. Bibcode:1987Natur.327..473S. doi:10.1038/327473a0. PMID   3587367. S2CID   4280158.
  28. ↑ Johnson, George (November 25, 1990). "Once Again, A MAN WITH A MISSION". The New York Times.
  29. ↑ "AIDS Experiment Based on Salk's Theories". The New York Times. February 12, 1988.
  30. ↑ Martinez, L. Joel (December 2000). "Remune Rejected: Will a Manual Recount Be Required?". The Center for AIDS Information & Advocacy.
  31. ↑ Kahn, James O.; Cherng, DW; Mayer, K; Murray, H; Lagakos, S (1 November 2000). "Evaluation of HIV-1 Immunogen, an Immunologic Modifier, Administered to Patients Infected With HIV Having 300 to 549 × 106/L CD4 Cell Counts: A Randomized Controlled Trial". JAMA. 284 (17): 2193–2302. doi:10.1001/jama.284.17.2193. PMID   11056590.
  32. ↑ Walker, Bruce, AIDS Vaccine Induces HIV-specific Immune Response In Chronic Infection, Massachusetts General Hospital, published in Science News, May 26, 2003, https://www.sciencedaily.com/releases/2003/05/030526104653.htm
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