A new type of personalized immunotherapy, known as adoptive T cell therapy shows striking results in several women with advanced cervical cancer. In a small, federally funded Phase II study which was supported by the National Cancer Institute and the National Institutes of Health, two patients with advanced cervical cancer and widespread metastases had complete remissions after a single treatment with the HPV-targeted T cells. These two patients have been cancer free for nearly a year.
Epidemiologic studies have convincingly demonstrate that the major risk factor for development of pre invasive as well as invasive carcinoma of the cervix is infection with the human papillomavirus or HPV which is usually passed on during direct skin-to-skin contact, most commonly sex. This makes HPV is the most common sexually transmitted disease in the United States. [1][2]
Cervical cancer, which forms in tissues of the cervix, the organ connecting the uterus and vagina, is usually a slow-growing cancer that may not have symptoms but can be found with regular Pap tests.
...this proof-of-principal study shows that adoptive transfer of HPV-targeted T cells can cause complete remission of metastatic cervical cancer…
Proof-of-principle
?This proof-of-principal study shows that adoptive transfer of HPV-targeted T cells can cause complete remission of metastatic cervical cancer. This remission can be long-lasting,? explained the study’s lead author Christian Hinrichs, MD, an assistant clinical investigator at the National Cancer Institute in Bethesda, MD. ?One implication of the study is that cellular therapy might have application to a broader range of tumor types than previously recognized. This treatment is still considered experimental and is associated with significant side effects. We also need to explore why this therapy worked so well in certain women, and not in others.? [3]
Limited treatment options
Women with metastatic cervical cancer ? caused by the human papillomavirus or HPV ? have limited treatment options. The median survival with the two standard first-line therapies, chemotherapy and a combination of chemotherapy and bevacizumab (Avastin?; Genentech/Roche,South San Francisco, CA 94080, USA), is 13 and 17 months, respectively. To date there is no second-line treatments available that improves survival.
Using the power of the Immune system
Adoptive T cell therapy uses the power of the immune system by recruiting the body’s own T cells. T cells travel through the body are are using their receptors to scan for small bits of protein called antigens on the surface of foreign cells. Only when an antigen matches the receptors, the T cell actually activates and launches an attack. Malignant cells are considered an ideal targets for T cells.
HPV-targeted adoptive T cell therapy essentially augments the natural immune response to HPV in the tumor. To develop the therapy, HPV-targeted T cells or immune cells that specifically attack tumor cells harboring HPV proteins, are grown from a patient?s tumor in the laboratory. Those cells are subsequently infused back into the patient to fight the cancer. This is the first time adoptive T cell therapy has been tested in cervical cancer. This kind of therapy has previously shown promise in the treatment of other cancers, including melanoma, leukemia, and sarcoma.
Study design
In the study, nine patients received adoptive T cell therapy, and three responded to the treatment. One patient had a partial response, with a 39% reduction in tumor volume, and two patients had complete remissions. Those two patients had widespread metastases, and the disease had progressed despite prior therapy. At the time of analysis, those patients remained in remission for 11 and 18 months after treatment. The treatment was associated with serious side effects, the most common being low blood counts, infections, and metabolic disorders.[3]
Based on the results at this time, researchers are planning to expand this study to enroll additional patients. The same study is also exploring adoptive T cell therapy for treatment of other HPV-related cancers, such as throat cancer and anal cancer.
Adoptive T cell therapy is being offered at an increasing number of major medical centers in the United States and other countries. More than 4,000 women die of cervical cancer each year in the United States. The disease disproportionately affects underserved populations. One reason why these populations see a higher proportion of patients with the disease is that they are less likely to undergo cervical cancer screenings. An other observation is that most patients are younger. Along with screening and preventative vaccines, better treatments are needed to reduce cervical cancer deaths in the future.
?These novel treatments are needed for women with recurrent or metastatic cervical cancer. Because of the association between cervical cancer and the HPV virus, adoptive immunotherapy is a promising approach for these patients,? explained Don S. Dizon, MD, FACP, an ASCO Expert, Assistant in Medicine, Medical Gynecologic Oncology at the Massachusetts General Hospitalin Boston, MA, and an advisory board member of Onco’Zine – The International Oncology Network and ADC Review/Journal of Antibody-drug Conjugates. ?The preliminary data demonstrate, not only the viability of this approach, but also that gains in survival can be realized in a cancer where patients have little to no effective treatment options and where median survival is usually less than two years.?
For more information:
[1] Schiffman MH, Bauer HM, Hoover RN, et al.: Epidemiologic evidence showing that human papillomavirus infection causes most cervical intraepithelial neoplasia. J Natl Cancer Inst 85 (12): 958-64, 1993.[Article][PubMed]
[2] Brisson J, Morin C, Fortier M, et al.: Risk factors for cervical intraepithelial neoplasia: differences between low- and high-grade lesions. Am J Epidemiol 140 (8): 700-10, 1994.[Article][PubMed]
[3] Hinrichs CS, Stevanovic S, Draper L, Somerville R, Wunderlich J, Restifo NP, Sherry R, et al. HPV-targeted tumor-infiltrating lymphocytes for cervical cancer. 2014 ASCO Annual Meeting. Oral Abstract Session, Tuesday June 3, 9:45 AM to 12:45 PM. Abstract No: LBA3008 Citation: J Clin Oncol 32:5s, 2014 (suppl; abstr LBA3008).[Abstract]
Photo: Christian Hinrichs, MD, at the American Society of Clinical Oncology Annual Meeting, Tuesday June 3, 2014. Photo Courtesy: ?ASCO/Zach Boyden-Holmes
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