Neuvenge

Neuvenge, Lapuleucel-T (APC 8024), is a therapeutic cancer vaccine (TCV) in development (clinical trial) 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,^[1][2] and is now scheduled to be tested on bladder cancer patients.^[3][4]

History

The concept of immunotherapy for cancer has been known for hundreds of years and was used by Dr William Coley et al. in the 1800s.^[5] Coley's Toxins are still available outside of the US. The idea of harnessing the antigen presenting cells (APC)'s to recognize cancer and target tumor cells for apoptosis (cell death) by the CD8 (cytotoxic cells) is a common approach to cancer vacine researchers. This 1997 example article describes targeting EGFR and other cell products and attaching their antigens to the CD64 receptor cells also using GM-CSF to grow more cells.^[6] The NIH calls this topic "Biological response modifiers (BRMs) occur naturally in the body and can be produced in the laboratory. BRMs alter the interaction between the body's immune defenses and cancer cells to boost, direct, or restore the body's ability to fight the disease." ^[7] Immunocompromising diseases have caused many deaths in human history. An ongoing example is Karposi's sarcoma (KS) caused by the Human herpesvirus 8 virus normally controlled by the body's immune system. KS is normally a rare diseaae but AIDS has made it all to commonplace. AIDS patients, whose immune system has been compromised, fall victim to serious opportunistic infections such as (TB) and KS. The movie "Philadelphia (film)" gives a dramatic representation of AIDS and KS. A good method of preventing some cancers is to stop the viruses that lead to them. This is known as prophylatic treatment. The current cancer prophylactic vaccines are for HVB (hepatitus "B" virus), HPV (cervical cancer, vaginal, vulvar cancer, penile, anal cancer) and HPV-positive oropharyngeal cancer are all defenses utilizing immunotherapy against viruses that lead to cancer.

Milestones

"A successful (TCV) is considered a milestone for cancer immunotherapy." ^[8] The only approved TCVs, as of 2010, are Provenge in the US and Oncogene in Russia. DNDN's future will require a different skill set to manage the mass production of this first-of-a-kind product. There are 32,000+/yr deaths from prostate cancer (CaP) in the US and that is only those with metastatic CRPC. If most of these patients were to receive this product that would increase current 2,000 output 16X. When (If) the project is expanded to those whose CaP is still controlled by hormone therapy that number could easily quadruple for the US alone. Were this therapy to be used on ALL Prostate cancer patients as a monotherapy that's (120,000+/yr.in the US). If those who are still on hormone therapy the numbers are in the millions. There are currently 2,000,000+ CaP patients in the US. DNDN is busy building plants, which all require FDA approval, in Morris Plains, New Jersey, Atlanta, Georgia and (Los Angeles County, California area) Seal Beach, California (actually in Orange County, California) for large scale Provenge production.^[9] They are still seeking overseas partners for development offshore.

Prospects

DNDN have stated that their therapy is not a one-hit wonder and they plan to "move forward one Provenge-like new cancer treatment every year". This will demonstrate that they really have an immunotherapy platform approach to cancer.^[10]

Combinational therapy

Involves using:

• Primary care
  • surgery
  • radiation
• Adjuvant care
  • hormone deprevation for those cancers effected by sex steroids
  • chemotherapy
  • therapeutic vaccine therapy.^[11] Immunotherapy has added another tool or leg for Oncologist to fight cancer. This therapy could be a part of all the other therapys listed.

Neuvenge history

Neuvenge is still in preliminary clinical trials and is evolving as of 2011. First Neuvenge trials were performed on patients with metastatic breast, ovarian or colorectal cancer that expressed HER-2 (HER2/neu). Some patients with stable disease after week 48 received an additional "booster" treatment using the identical protocol. Lapuleucel-T is an investigational active immunotherapy product consisting of autologous peripheral blood mononuclear cells, including antigen presenting cells, which are cultured ex vivo with BA7072, a recombinant fusion antigen consisting of portions of the intracellular and extracellular regions of HER-2/neu linked to granulocyte-macrophage colony-stimulating factor. In a change of course, DNDN is planning a bladder cancer clinical trial using Neuvenge to begin 2011. ^[12] DNDN is also using ACI technology Active cellular immunotherapy ^[13] "This is a therapuetic platform using the patient's own cells to simulate an immune response." These are two major candidates:

• Carbonic anhydrase IX (CA9) for kidney, colon, cervical cancers
• Carcinoembryonic antigen (CEA) for breast, lung and colon cancers

References

1. ^ "Phase 1 Study Of Lapuleucel-T In Advanced Breast Cancer Patients Is Promising" (Press release). Dendreon Corporation. August 21, 2007. http://www.emaxhealth.com/98/15164.html. Retrieved January 14, 2011. 
2. ^ Peethambaram, P. P.; Melisko, M. E.; Rinn, K. J.; Alberts, S. R.; Provost, N. M.; Jones, L. A.; Sims, R. B.; Lin, L. R. C. et al. (2009). "A Phase I Trial of Immunotherapy with Lapuleucel-T (APC8024) in Patients with Refractory Metastatic Tumors that Express HER-2/neu". Clinical Cancer Research 15 (18): 5937–44. doi:10.1158/1078-0432.CCR-08-3282. PMC 2766354. PMID 19723649. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2766354. 
3. ^ "Dendreon Presents Integrated Analysis of Clinical Data from Neuvenge Trials at Chemotherapy Foundation Symposium" (Press release). Dendreon Corporation. November 6, 2008. http://www.drugs.com/clinical_trials/dendreon-presents-integrated-analysis-clinical-data-neuvenge-trials-chemotherapy-foundation-6089.html. Retrieved January 14, 2011. 
4. ^ Lapuleucel-T | Singularity Hub^{[unreliable medical source?]}
5. ^ http://www.oncbiz.com/documents/OBR_JAN10_CV.pdf
6. ^ Curnow, Randall T. (1997). "Clinical experience with CD64-directed immunotherapy. An overview". Cancer Immunology, Immunotherapy 45: 210–5. doi:10.1007/s002620050435. PMID 9435876. 
7. ^ Biological Therapies for Cancer: Q & A - National Cancer Institute
8. ^ Dendritic Cell Immunotherapy - The Provenge Prostate Cancer Vaccine
9. ^ Review Memo of the 483 Responses for the 2010 PLI at Dendreon’s Manufacturing Facility for Sipuleucel-T at Morris Plains, New Jersey - Provenge
10. ^ Dendreon to Turn in Provenge Application to FDA in Mid-November | Xconomy
11. ^ Doehn, Christian; Böhmer, Torsten; Kausch, Ingo; Sommerauer, Martin; Jocham, Dieter (2008). "Prostate cancer vaccines: current status and future potential". BioDrugs 22 (2): 71–84. PMID 18345705. http://content.wkhealth.com/linkback/openurl?issn=1173-8804&volume=22&issue=2&spage=71. 
12. ^ Cancer Treatment, Active Cellular Immunotherapy - Dendreon.com
13. ^ ACI Product Candidate - Ovarian, Colon Cancer Treatment - Dendreon.com