Long-term vaccine therapy with autologous whole tumor cell-pulsed dendritic cells for a patient with recurrent rectal carcinoma
ABSTRACT
We performed continuous dendritic cells (DCs) vaccination to treat a patient with chemotherapy-resistant recurrent rectal carcinoma and lung and bone metastases. A patient has received a total of 66 DC vaccinations at 14-day intervals for 3 years until his death. Necrotic whole tumor cells (WTC) were selected as the tumor-associated antigen source because they showed a greater capacity for DC maturation and interleukin-12 secretion than both necrotic tumor lysate alone and necrotic tumor cell fragment alone. After the sixth vaccination, both skin test and interferon-γ (IFN-γ) enzyme-linked immunospot (ELISPOT) response by peripheral blood T-cells to WTC-pulsed DCs were positive. Importantly, T-cell responses were positive towards DCs pulsed with several synthetic peptides including Carcinoembryonic antigen (CEA), Melanoma associated antigen (MAGE)1 and MAGE3. A biopsy specimen collected from the pelvic bone metastasis after the 6th vaccination showed marked necrotic change of the carcinoma cells, with many infiltrating mononuclear cells. The patient did not show any particular adverse reactions to vaccination such as autoimmune phenomena. Our experience of this case suggests that continuous long-term vaccination with autologous WTC-pulsed DCs can elicit in vivo T-cell response against multiple tumor-associated antigens and induce tumor regression in disease that has proven resistant to intensive chemo- or radiation therapy.