Immunotherapy of Recurrent Cervical Cancers Using Dendritic Cells (DCs)
Immunotherapy of Recurrent Cervical Cancers Using Dendritic Cells (DCs)
Chemotherapy is the current standard treatment for unresectable recurrent cervical carcinoma
 after radiotherapy or distant metastasis of cervical carcinoma. The most effective regimens
 are cisplatin-based chemotherapy. After failure of the cisplatin-based chemotherapy, there is
 still no treatment that has been proved to be effective.

 Human papilloma viruses (HPV) have been consistently implicated in causing cervical cancer
 especially those high-risk types (HPV 16,18,31,45) have been strongly associated with
 cervical cancer. HPV 16 was found in more than 50% of cervical cancer tissues. Results from
 many animal tumor models have indicated that immunization with tumor antigen-pulsed dendritic
 cells can trigger a long-lasting anti-tumor immune response and significantly inhibit the
 growth of implanted tumor cells. Recently, many clinical trials have been conducted to
 evaluate the feasibility and safety of immunizing cancer patients with tumor antigen-pulsed
 dendritic cells. No severe toxicity has been reported and some patients were shown to respond
 to the treatment. Based on previous animal and clinical studies by other investigators, we
 propose to evaluate the potential of immunizing cancer patients with antigen-pulsed
 autologous dendritic cells as a cancer vaccine to treat for recurrent cervical cancers after
 failure of cisplatin-based chemotherapy treatment or refusing chemotherapy. In this study, we
 will generate dendritic cells by culturing patient's autologous PBMC with GM-CSF and IL-4 in
 vitro. These dendritic cells will be pulsed with synthetic peptides representing the CTL
 epitopes on HPV Type 16 E7. Antigen-pulsed dendritic cells will be injected into inguinal
 lymph nodes under the guidance of real-time sonography. Each patient will receive four
 injections and 12 patients in total will be recruited for this study.
Chemotherapy is the current standard treatment for unresectable recurrent cervical carcinoma
 after radiotherapy or distant metastasis of cervical carcinoma. The most effective regimens
 are cisplatin-based chemotherapy. After failure of the cisplatin-based chemotherapy, there is
 still no treatment that has been proved to be effective.

 Human papilloma viruses (HPV) have been consistently implicated in causing cervical cancer
 especially those high-risk types (HPV 16,18,31,45) have been strongly associated with
 cervical cancer. HPV 16 was found in more than 50% of cervical cancer tissues. Results from
 many animal tumor models have indicated that immunization with tumor antigen-pulsed dendritic
 cells can trigger a long-lasting anti-tumor immune response and significantly inhibit the
 growth of implanted tumor cells. Recently, many clinical trials have been conducted to
 evaluate the feasibility and safety of immunizing cancer patients with tumor antigen-pulsed
 dendritic cells. No severe toxicity has been reported and some patients were shown to respond
 to the treatment. Based on previous animal and clinical studies by other investigators, we
 propose to evaluate the potential of immunizing cancer patients with antigen-pulsed
 autologous dendritic cells as a cancer vaccine to treat for recurrent cervical cancers after
 failure of cisplatin-based chemotherapy treatment or refusing chemotherapy. In this study, we
 will generate dendritic cells by culturing patient's autologous PBMC with GM-CSF and IL-4 in
 vitro. These dendritic cells will be pulsed with synthetic peptides representing the CTL
 epitopes on HPV Type 16 E7. Antigen-pulsed dendritic cells will be injected into inguinal
 lymph nodes under the guidance of real-time sonography. Each patient will receive four
 injections and 12 patients in total will be recruited for this study.
Inclusion Criteria:

 1. recurrent cervical cancer

 2. HPV 16 infection

 3. Previously received cisplatin ot 5-FU based chemotherapy or refused to receive
 chemotherapy

 4. HLA-A2 haplotype

 5. Older than 20 years old

 6. ECOG I or II

 7. Life expectancy longer than 3 months

 8. Adequate bone marrow reserve

 9. pregnancy test: negative

 10. Informed consent obtained

 Exclusion Criteria:

 1. CNS metastasis

 2. Acute or chronic infection

 3. Pregnant or lactating women

 4. Asthma

 5. Cardiac diseases such as heart failure, unstable angina, arrhythmia, myocardial
 infarction

 6. Autoimmune disease

 7. Previously other cancers (except basal cell cancer)

 8. Without chemotherapy, biotherapy for more than 6 weeks