A Phase I Cancer Vaccine Study for Patients With Metastatic Breast Cancer

Summary

The study uses a molecule or particle that is found only on cancer cells and is unique to cancer cells, as it is not detected on normal tissue. The molecule is known as "oncofetal antigen" or OFA. Because OFA is unique to cancer, the investigators feel OFA could be used to educate the patients' own defenses to more effectively fight the cancer on her own, he or she is harboring. Although investigators found OFA to be present in large concentrations on all cancers, it was found to be especially abundant in breast cancers. Therefore, the investigators feel that this molecule would be a good target for stimulating patient defenses especially against breast cancer cells. To accomplish this, certain defense cells (immune cells) will be washed out from the patients' blood using a machine to which the patient is connected through two small cannulas placed into veins located in the patients' arms. Those cells will be manipulated in the laboratory with artificially engineered OFA. These "reeducated" cells will be injected into the skin of patients. There will be a series of three skin injections in 4 week intervals. It is hoped that this treatment will convert the patients' defenses to a point that effective anti cancer responses will be induced. Effectiveness of the treatment will be monitored with blood tests and assessment of the size of the cancers.

Timeline

Start

2008-05

Primary completion

2010-02

Completion

2015-02

Publications

• Background Holtl L, Zelle-Rieser C, Gander H, Papesh C, Ramoner R, Bartsch G, Rogatsch H, Barsoum AL, Coggin JH Jr, Thurnher M. Immunotherapy of metastatic renal cell carcinoma with tumor lysate-pulsed autologous dendritic cells. Clin Cancer Res. 2002 Nov;8(11):3369-76.
• Background Rohrer JW, Barsoum AL, Dyess DL, Tucker JA, Coggin JH Jr. Human breast carcinoma patients develop clonable oncofetal antigen-specific effector and regulatory T lymphocytes. J Immunol. 1999 Jun 1;162(11):6880-92.
• Background Coggin JH Jr, Barsoum AL, Rohrer JW. 37 kiloDalton oncofetal antigen protein and immature laminin receptor protein are identical, universal T-cell inducing immunogens on primary rodent and human cancers. Anticancer Res. 1999 Nov-Dec;19(6C):5535-42.
• Background Zelle-Rieser C, Barsoum AL, Sallusto F, Ramoner R, Rohrer JW, Holtl L, Bartsch G, Coggin JH JR, Thurnher M. Expression and immunogenicity of oncofetal antigen-immature laminin receptor in human renal cell carcinoma. J Urol. 2001 May;165(5):1705-9.
• Background Coggin JH Jr. Classification of tumor-associated antigens in rodents and humans. Immunol Today. 1994 May;15(5):246-7. doi: 10.1016/0167-5699(94)90251-8. No abstract available.
• Background Barsoum AL, Coggin JH Jr. Isolation and partial characterization of a soluble oncofetal antigen from murine and human amniotic fluids. Int J Cancer. 1991 May 10;48(2):248-52. doi: 10.1002/ijc.2910480216.
• Background Payne WJ Jr, Coggin JH Jr. Mouse monoclonal antibody to embryonic antigen: development, cross-reactivity with rodent and human tumors, and preliminary polypeptide characterization. J Natl Cancer Inst. 1985 Sep;75(3):527-44.
• Background Barsoum AL, Coggin JH Jr. Immunogenicity of a soluble partially purified oncofetal antigen from murine fibrosarcoma in syngeneic mice. J Biol Response Mod. 1989 Dec;8(6):579-92.
• Background Coggin JH Jr, Barsoum AL, Rohrer JW. Tumors express both unique TSTA and crossprotective 44 kDa oncofetal antigen. Immunol Today. 1998 Sep;19(9):405-8. doi: 10.1016/s0167-5699(98)01305-x. No abstract available.
• Background Gussack GS, Rohrer SD, Hester RB, Liu PI, Coggin JH Jr. Human squamous cell carcinoma lines express oncofetal 44-kD polypeptide defined by monoclonal antibody to mouse fetus. Cancer. 1988 Jul 15;62(2):283-90. doi: 10.1002/1097-0142(19880715)62:23.0.co;2-o.
• Background Coggin JH Jr, Rohrer SD, Hester RD, Barsoum AL, Rashid HU, Gussack GS. 44-kd oncofetal transplantation antigen in rodent and human fetal cells. Implications of recrudescence in human and rodent cancers. Arch Otolaryngol Head Neck Surg. 1993 Nov;119(11):1257-66. doi: 10.1001/archotol.1993.01880230105015.
• Background Coggin JH Jr. Oncofetal antigens. Nature. 1986 Jan 30-Feb 5;319(6052):428. doi: 10.1038/319428c0. No abstract available.
• Background Coggin JH Jr, Rohrer JW, Barsoum AL. True immunogenicity of oncofetal antigen/immature laminin receptor protein. Cancer Res. 2004 Jul 1;64(13):4685; author reply 4685. doi: 10.1158/0008-5472.CAN-03-2940. No abstract available.
• Background Rohrer JW, Barsoum AL, Coggin JH Jr. Identification of oncofetal antigen/immature laminin receptor protein epitopes that activate BALB/c mouse OFA/iLRP-specific effector and regulatory T cell clones. J Immunol. 2006 Mar 1;176(5):2844-56. doi: 10.4049/jimmunol.176.5.2844.
• Background Coggin JH Jr. Embryonic antigens in malignancy and pregnancy: common denominators in immune regulation. Ciba Found Symp. 1983;96:28-54. doi: 10.1002/9780470720776.ch3.
• Background Rohrer JW, Culpepper C, Barsoum AL, Coggin JH Jr. Characterization of RFM mouse T lymphocyte anti-oncofetal antigen immunity in apparent tumor-free, long-term survivors of sublethal X-irradiation by limiting dilution T lymphocyte cloning. J Immunol. 1995 Mar 1;154(5):2266-80.
• Background Rohrer JW, Coggin JH Jr. CD8 T cell clones inhibit antitumor T cell function by secreting IL-10. J Immunol. 1995 Dec 15;155(12):5719-27.

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