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Therapeutic response in patients with advanced malignancies treated with combined dendritic cell-activated T cell based immunotherapy and intensity-modulated radiotherapy.

Hasumi K, Aoki Y, Watanabe R, Hankey KG, Mann DL - Cancers (Basel) (2011)

Bottom Line: Successful cancer immunotherapy is confounded by the magnitude of the tumor burden and the presence of immunoregulatory elements that suppress an immune response.We hypothesized that radiation would lower the tumor burdens, decrease the number/function of regulatory cells in the tumor environment, and release products of tumor cells that could be acquired by intratumoral injected immature dendritic cells (iDC).These results demonstrate the safety and effectiveness of this multimodality strategy combining immunotherapy and IMRT in patients with advanced malignancies.

View Article: PubMed Central - PubMed

Affiliation: Hasumi International Research Foundation, Tokyo Research Center, 1-44-6 Asagaya-kita, Suginami- ku, Tokyo 166-0001, Japan. dmann001@umaryland.edu.

ABSTRACT
Successful cancer immunotherapy is confounded by the magnitude of the tumor burden and the presence of immunoregulatory elements that suppress an immune response. To approach these issues, 26 patients with advanced treatment refractory cancer were enrolled in a safety/feasibility study wherein a conventional treatment modality, intensity modulated radiotherapy (IMRT), was combined with dendritic cell-based immunotherapy. We hypothesized that radiation would lower the tumor burdens, decrease the number/function of regulatory cells in the tumor environment, and release products of tumor cells that could be acquired by intratumoral injected immature dendritic cells (iDC). Metastatic lesions identified by CT (computed tomography) were injected with autologous iDC combined with a cytokine-based adjuvant and KLH (keyhole limpet hemocyanin), followed 24 h later by IV-infused T-cells expanded with anti-CD3 and IL-2 (AT). After three to five days, each of the injected lesions was treated with fractionated doses of IMRT followed by another injection of intratumoral iDC and IV-infused AT. No toxicity was observed with cell infusion while radiation-related toxicity was observed in seven patients. Five patients had progressive disease, eight demonstrated complete resolution at treated sites but developed recurrent disease at other sites, and 13 showed complete response at various follow-up times with an overall estimated Kaplan-Meier disease-free survival of 345 days. Most patients developed KLH antibodies supporting our hypothesis that the co-injected iDC are functional with the capacity to acquire antigens from their environment and generate an adaptive immune response. These results demonstrate the safety and effectiveness of this multimodality strategy combining immunotherapy and IMRT in patients with advanced malignancies.

No MeSH data available.


Related in: MedlinePlus

Kaplan-Meier analysis comparing the number of disease-free days of all patients with those that did or did not develop anti-KLH antibodies.
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f5-cancers-03-02223: Kaplan-Meier analysis comparing the number of disease-free days of all patients with those that did or did not develop anti-KLH antibodies.

Mentions: Interestingly, the frequency of KLH immunity was higher in the complete response group (81.82%) than in the combined recurrent and progressive disease groups (58.33%). To determine if KLH responses were correlated with response to therapy, Kaplan-Meier analysis of disease-free survival of the two groups were compared (Figure 5). The data suggest that the patients who responded to KLH immunization had a better overall survival. However, the difference was not statistically significant (p = 0.31) when analyzed using the exact log-rank test from StatXact.


Therapeutic response in patients with advanced malignancies treated with combined dendritic cell-activated T cell based immunotherapy and intensity-modulated radiotherapy.

Hasumi K, Aoki Y, Watanabe R, Hankey KG, Mann DL - Cancers (Basel) (2011)

Kaplan-Meier analysis comparing the number of disease-free days of all patients with those that did or did not develop anti-KLH antibodies.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3757414&req=5

f5-cancers-03-02223: Kaplan-Meier analysis comparing the number of disease-free days of all patients with those that did or did not develop anti-KLH antibodies.
Mentions: Interestingly, the frequency of KLH immunity was higher in the complete response group (81.82%) than in the combined recurrent and progressive disease groups (58.33%). To determine if KLH responses were correlated with response to therapy, Kaplan-Meier analysis of disease-free survival of the two groups were compared (Figure 5). The data suggest that the patients who responded to KLH immunization had a better overall survival. However, the difference was not statistically significant (p = 0.31) when analyzed using the exact log-rank test from StatXact.

Bottom Line: Successful cancer immunotherapy is confounded by the magnitude of the tumor burden and the presence of immunoregulatory elements that suppress an immune response.We hypothesized that radiation would lower the tumor burdens, decrease the number/function of regulatory cells in the tumor environment, and release products of tumor cells that could be acquired by intratumoral injected immature dendritic cells (iDC).These results demonstrate the safety and effectiveness of this multimodality strategy combining immunotherapy and IMRT in patients with advanced malignancies.

View Article: PubMed Central - PubMed

Affiliation: Hasumi International Research Foundation, Tokyo Research Center, 1-44-6 Asagaya-kita, Suginami- ku, Tokyo 166-0001, Japan. dmann001@umaryland.edu.

ABSTRACT
Successful cancer immunotherapy is confounded by the magnitude of the tumor burden and the presence of immunoregulatory elements that suppress an immune response. To approach these issues, 26 patients with advanced treatment refractory cancer were enrolled in a safety/feasibility study wherein a conventional treatment modality, intensity modulated radiotherapy (IMRT), was combined with dendritic cell-based immunotherapy. We hypothesized that radiation would lower the tumor burdens, decrease the number/function of regulatory cells in the tumor environment, and release products of tumor cells that could be acquired by intratumoral injected immature dendritic cells (iDC). Metastatic lesions identified by CT (computed tomography) were injected with autologous iDC combined with a cytokine-based adjuvant and KLH (keyhole limpet hemocyanin), followed 24 h later by IV-infused T-cells expanded with anti-CD3 and IL-2 (AT). After three to five days, each of the injected lesions was treated with fractionated doses of IMRT followed by another injection of intratumoral iDC and IV-infused AT. No toxicity was observed with cell infusion while radiation-related toxicity was observed in seven patients. Five patients had progressive disease, eight demonstrated complete resolution at treated sites but developed recurrent disease at other sites, and 13 showed complete response at various follow-up times with an overall estimated Kaplan-Meier disease-free survival of 345 days. Most patients developed KLH antibodies supporting our hypothesis that the co-injected iDC are functional with the capacity to acquire antigens from their environment and generate an adaptive immune response. These results demonstrate the safety and effectiveness of this multimodality strategy combining immunotherapy and IMRT in patients with advanced malignancies.

No MeSH data available.


Related in: MedlinePlus