GM2-KLH Conjugate Vaccine: Increased Immunogenicity in Melanoma Patients after Administration with Immunological Adjuvant QS-21 Export

@article{helling:95xx, abstract = {The cell surface gangliosides GM2, GD2, and GD3 are often overexpressed in malignant melanoma. We have shown previously that immunization of melanoma patients with GM2 and Bacillus Calmette-Guerin induced an IgM antibody response in most patients and that patients with high titer GM2 antibodies showed increased survival. As is commonly seen with carbohydrate antigens (which are T independent), the IgM response was short lived, and an IgG response was rarely observed. To increase immunogenicity, we conjugated GM2 covalently with keyhole limpet hemocyanin (KLH). GM2-KLH vaccine was given to melanoma patients alone or with one of the three adjuvants: Bacillus Calmette-Guerin, DE-TOX, or QS-21. The most effective vaccine was GM2-KLH with QS-21. It induced a much higher titer, a longer-lasting IgM GM2 antibody response, and a consistent IgG response (isotype IgG1 and IgG3). It also induced the highest titer anti-KLH response. The results suggest that the conjugate GM2-KLH plus QS-21 vaccine elicited significant T-cell help. Because there was no serious toxicity, this vaccine approach is attractive for augmenting the immunogenicity of other gangliosides, such as GD2 and GD3, and to determine the effects of ganglioside antibodies on the course of melanoma. In addition, the finding that QS-21 significantly increased the immunogenicity of GM2-KLH suggests that it may do the same for other conjugate vaccines, many of which are currently used without adjuvant.}, author = {Helling, Friedhelm and Zhang, Shengle and Shang, Ann and Adluri, Sucharita and Calves, Michele and Koganty, Rao and Longenecker, Michael B. and Yao, Tzy-J and Oettgen, Herbert F. and Livingston, Philip O.}, citeulike-article-id = {3521020}, citeulike-linkout-0 = {http://cancerres.aacrjournals.org/cgi/content/abstract/55/13/2783}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/7796403}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=7796403}, day = {1}, journal = {Cancer Res}, keywords = {saponins}, month = {July}, number = {13}, pages = {2783--2788}, posted-at = {2008-11-16 04:30:46}, priority = {2}, title = {GM2-KLH Conjugate Vaccine: Increased Immunogenicity in Melanoma Patients after Administration with Immunological Adjuvant QS-21}, url = {http://cancerres.aacrjournals.org/cgi/content/abstract/55/13/2783}, volume = {55}, year = {1995} }

TY - JOUR ID - helling:95xx L3 - citeulike-article-id:3521020 N2 - The cell surface gangliosides GM2, GD2, and GD3 are often overexpressed in malignant melanoma. We have shown previously that immunization of melanoma patients with GM2 and Bacillus Calmette-Guerin induced an IgM antibody response in most patients and that patients with high titer GM2 antibodies showed increased survival. As is commonly seen with carbohydrate antigens (which are T independent), the IgM response was short lived, and an IgG response was rarely observed. To increase immunogenicity, we conjugated GM2 covalently with keyhole limpet hemocyanin (KLH). GM2-KLH vaccine was given to melanoma patients alone or with one of the three adjuvants: Bacillus Calmette-Guerin, DE-TOX, or QS-21. The most effective vaccine was GM2-KLH with QS-21. It induced a much higher titer, a longer-lasting IgM GM2 antibody response, and a consistent IgG response (isotype IgG1 and IgG3). It also induced the highest titer anti-KLH response. The results suggest that the conjugate GM2-KLH plus QS-21 vaccine elicited significant T-cell help. Because there was no serious toxicity, this vaccine approach is attractive for augmenting the immunogenicity of other gangliosides, such as GD2 and GD3, and to determine the effects of ganglioside antibodies on the course of melanoma. In addition, the finding that QS-21 significantly increased the immunogenicity of GM2-KLH suggests that it may do the same for other conjugate vaccines, many of which are currently used without adjuvant. IS - 13 JF - Cancer Res EP - 2788 TI - GM2-KLH Conjugate Vaccine: Increased Immunogenicity in Melanoma Patients after Administration with Immunological Adjuvant QS-21 VL - 55 SP - 2783 KW - saponins AU - Helling, Friedhelm AU - Zhang, Shengle AU - Shang, Ann AU - Adluri, Sucharita AU - Calves, Michele AU - Koganty, Rao AU - Longenecker, Michael AU - Yao, Tzy-J AU - Oettgen, Herbert AU - Livingston, Philip PY - 1995/07/01/ UR - http://cancerres.aacrjournals.org/cgi/content/abstract/55/13/2783 ER -