Tags

Type your tag names separated by a space and hit enter

Immunotherapy with tumor-targeted superantigens (TTS) in combination with docetaxel results in synergistic anti-tumor effects.
Int Immunopharmacol. 2009 Aug; 9(9):1063-70.II

Abstract

In this study we explored the possibility of combining immunotherapy against cancer with the well-established cytostatic drug docetaxel. Tumor-targeted superantigens (TTS) utilizes the powerful T cell activating property of a superantigen such as staphylococcal enterotoxin A (SEA) in fusion with an anti-tumor Fab-fragment to target this T cell activity against tumor cells. TTS fusion proteins are efficient in a number of experimental tumor models including the B16 mouse melanoma transfected with a human tumor-associated antigen (GA733-2 or EpCam) recognized by the C215 monoclonal antibody. The distinct mechanisms of action of TTS and docetaxel provide the prerequisites for successful combination treatment. However, as a result of the anti-proliferative properties of cytostatic drugs, chemotherapy may modify TTS induced immune activation during combination treatment. Here we evaluated the anti-tumor effects of combining C215Fab-SEA with docetaxel against B16-C215 tumors growing in the lung of C57Bl/6 mice. Both compounds generated a significant reduction in the number of B16-C215 lung tumors when administered alone. Prior treatment with docetaxel at therapeutic doses did not interfere with superantigen induced T cell activation but rather appeared to enhance the response, while simultaneous treatment was suppressive. Combining TTS and docetaxel significantly improved tumor therapy, further reducing the number of lung tumors as compared to mono therapies. Importantly, the combination treatment at timely settings synergistically prolonged long term survival in B16-C215 tumor bearing mice. The results of this study demonstrate that TTS immunotherapy is highly compatible with docetaxel and suggest a significant potential of the combination for human cancer therapy.

Authors+Show Affiliations

Active Biotech Research AB, Lund, Sweden. anette.sundstedt@activebiotech.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19410661

Citation

Sundstedt, Anette, et al. "Immunotherapy With Tumor-targeted Superantigens (TTS) in Combination With Docetaxel Results in Synergistic Anti-tumor Effects." International Immunopharmacology, vol. 9, no. 9, 2009, pp. 1063-70.
Sundstedt A, Celander M, Ohman MW, et al. Immunotherapy with tumor-targeted superantigens (TTS) in combination with docetaxel results in synergistic anti-tumor effects. Int Immunopharmacol. 2009;9(9):1063-70.
Sundstedt, A., Celander, M., Ohman, M. W., Forsberg, G., & Hedlund, G. (2009). Immunotherapy with tumor-targeted superantigens (TTS) in combination with docetaxel results in synergistic anti-tumor effects. International Immunopharmacology, 9(9), 1063-70. https://doi.org/10.1016/j.intimp.2009.04.013
Sundstedt A, et al. Immunotherapy With Tumor-targeted Superantigens (TTS) in Combination With Docetaxel Results in Synergistic Anti-tumor Effects. Int Immunopharmacol. 2009;9(9):1063-70. PubMed PMID: 19410661.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Immunotherapy with tumor-targeted superantigens (TTS) in combination with docetaxel results in synergistic anti-tumor effects. AU - Sundstedt,Anette, AU - Celander,Mona, AU - Ohman,Marie Wallén, AU - Forsberg,Göran, AU - Hedlund,Gunnar, Y1 - 2009/05/03/ PY - 2009/03/20/received PY - 2009/04/24/revised PY - 2009/04/27/accepted PY - 2009/5/5/entrez PY - 2009/5/5/pubmed PY - 2010/1/15/medline SP - 1063 EP - 70 JF - International immunopharmacology JO - Int. Immunopharmacol. VL - 9 IS - 9 N2 - In this study we explored the possibility of combining immunotherapy against cancer with the well-established cytostatic drug docetaxel. Tumor-targeted superantigens (TTS) utilizes the powerful T cell activating property of a superantigen such as staphylococcal enterotoxin A (SEA) in fusion with an anti-tumor Fab-fragment to target this T cell activity against tumor cells. TTS fusion proteins are efficient in a number of experimental tumor models including the B16 mouse melanoma transfected with a human tumor-associated antigen (GA733-2 or EpCam) recognized by the C215 monoclonal antibody. The distinct mechanisms of action of TTS and docetaxel provide the prerequisites for successful combination treatment. However, as a result of the anti-proliferative properties of cytostatic drugs, chemotherapy may modify TTS induced immune activation during combination treatment. Here we evaluated the anti-tumor effects of combining C215Fab-SEA with docetaxel against B16-C215 tumors growing in the lung of C57Bl/6 mice. Both compounds generated a significant reduction in the number of B16-C215 lung tumors when administered alone. Prior treatment with docetaxel at therapeutic doses did not interfere with superantigen induced T cell activation but rather appeared to enhance the response, while simultaneous treatment was suppressive. Combining TTS and docetaxel significantly improved tumor therapy, further reducing the number of lung tumors as compared to mono therapies. Importantly, the combination treatment at timely settings synergistically prolonged long term survival in B16-C215 tumor bearing mice. The results of this study demonstrate that TTS immunotherapy is highly compatible with docetaxel and suggest a significant potential of the combination for human cancer therapy. SN - 1878-1705 UR - https://www.unboundmedicine.com/medline/citation/19410661/Immunotherapy_with_tumor_targeted_superantigens__TTS__in_combination_with_docetaxel_results_in_synergistic_anti_tumor_effects_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1567-5769(09)00163-5 DB - PRIME DP - Unbound Medicine ER -