T-cell adoptive immunotherapy of metastatic renal cell carcinoma
Identifieur interne : 00AC61 ( Main/Exploration ); précédent : 00AC60; suivant : 00AC62T-cell adoptive immunotherapy of metastatic renal cell carcinoma
Auteurs : Gregory E. Plautz [États-Unis] ; Ronald M. Bukowski [États-Unis] ; Andrew C. Novick [États-Unis] ; Eric A. Klein [États-Unis] ; Elroy D. Kursh [États-Unis] ; Thomas E. Olencki [États-Unis] ; Randall J. Yetman [États-Unis] ; Andrew Pienkny [États-Unis] ; Kate Sandstrom [États-Unis] ; Suyu Shu [États-Unis]Source :
- Urology [ 0090-4295 ] ; 1999.
Abstract
Objectives. To determine the feasibility and toxicity of the adoptive transfer of ex vivo-activated T lymphocytes that have been sensitized to autologous tumor vaccine in vivo. Methods. Twenty patients with extensive metastatic renal cell carcinoma received systemic adoptive immunotherapy with autologous T cells in the absence of conjunctional interleukin-2 (IL-2) administration. Patients were vaccinated intradermally with irradiated autologous tumor cells and granulocyte-macrophage colony-stimulating factor as an adjuvant to stimulate an immune response. Inguinal lymph nodes draining the vaccine site were surgically removed, and the cells were stimulated with staphylococcal enterotoxin A followed by expansion in 60 IU/mL IL-2, and in some cases additionally stimulated with anti-CD3 monoclonal antibody and IL-2, to obtain a large number of cells. Results. The staphylococcal enterotoxin A/IL-2 activation induced vigorous proliferation of T cells (median expansion 26-fold) that were a mixture of CD4 and CD8 T lymphocytes. Activated cells were infused intravenously at doses ranging from 2 × 109 to 9.5 × 1010. There was minimal toxicity consisting of grade 1 or 2 fever and nausea, and the entire treatment was delivered as outpatient therapy. One patient had a partial response, one had a mixed response, and 8 had stable disease lasting at least 5 months. Conclusions. Adoptive transfer of ex vivo-activated, tumor vaccine-primed lymph node cells is feasible and is associated with minimal toxicity when used alone. These results warrant further study in a Phase II trial.
Url:
DOI: 10.1016/S0090-4295(99)00303-9
Affiliations:
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Plautz</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Surgery Research, Cleveland Clinic Foundation, Cleveland, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Bukowski, Ronald M" sort="Bukowski, Ronald M" uniqKey="Bukowski R" first="Ronald M" last="Bukowski">Ronald M. Bukowski</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Experimental Therapeutics Program, Cleveland Clinic Foundation, Cleveland, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Novick, Andrew C" sort="Novick, Andrew C" uniqKey="Novick A" first="Andrew C" last="Novick">Andrew C. Novick</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Urology, Cleveland Clinic Foundation, Cleveland, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Klein, Eric A" sort="Klein, Eric A" uniqKey="Klein E" first="Eric A" last="Klein">Eric A. Klein</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Experimental Therapeutics Program, Cleveland Clinic Foundation, Cleveland, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Kursh, Elroy D" sort="Kursh, Elroy D" uniqKey="Kursh E" first="Elroy D" last="Kursh">Elroy D. Kursh</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Urology, Cleveland Clinic Foundation, Cleveland, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Olencki, Thomas E" sort="Olencki, Thomas E" uniqKey="Olencki T" first="Thomas E" last="Olencki">Thomas E. Olencki</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Experimental Therapeutics Program, Cleveland Clinic Foundation, Cleveland, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Yetman, Randall J" sort="Yetman, Randall J" uniqKey="Yetman R" first="Randall J" last="Yetman">Randall J. Yetman</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Urology, Cleveland Clinic Foundation, Cleveland, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Pienkny, Andrew" sort="Pienkny, Andrew" uniqKey="Pienkny A" first="Andrew" last="Pienkny">Andrew Pienkny</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Urology, Cleveland Clinic Foundation, Cleveland, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Sandstrom, Kate" sort="Sandstrom, Kate" uniqKey="Sandstrom K" first="Kate" last="Sandstrom">Kate Sandstrom</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Surgery Research, Cleveland Clinic Foundation, Cleveland, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Shu, Suyu" sort="Shu, Suyu" uniqKey="Shu S" first="Suyu" last="Shu">Suyu Shu</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Surgery Research, Cleveland Clinic Foundation, Cleveland, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j">Urology</title><title level="j" type="abbrev">URL</title><idno type="ISSN">0090-4295</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1999">1999</date><biblScope unit="volume">54</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="617">617</biblScope><biblScope unit="page" to="623">623</biblScope></imprint><idno type="ISSN">0090-4295</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0090-4295</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Objectives. To determine the feasibility and toxicity of the adoptive transfer of ex vivo-activated T lymphocytes that have been sensitized to autologous tumor vaccine in vivo. Methods. Twenty patients with extensive metastatic renal cell carcinoma received systemic adoptive immunotherapy with autologous T cells in the absence of conjunctional interleukin-2 (IL-2) administration. Patients were vaccinated intradermally with irradiated autologous tumor cells and granulocyte-macrophage colony-stimulating factor as an adjuvant to stimulate an immune response. Inguinal lymph nodes draining the vaccine site were surgically removed, and the cells were stimulated with staphylococcal enterotoxin A followed by expansion in 60 IU/mL IL-2, and in some cases additionally stimulated with anti-CD3 monoclonal antibody and IL-2, to obtain a large number of cells. Results. The staphylococcal enterotoxin A/IL-2 activation induced vigorous proliferation of T cells (median expansion 26-fold) that were a mixture of CD4 and CD8 T lymphocytes. Activated cells were infused intravenously at doses ranging from 2 × 109 to 9.5 × 1010. There was minimal toxicity consisting of grade 1 or 2 fever and nausea, and the entire treatment was delivered as outpatient therapy. One patient had a partial response, one had a mixed response, and 8 had stable disease lasting at least 5 months. Conclusions. Adoptive transfer of ex vivo-activated, tumor vaccine-primed lymph node cells is feasible and is associated with minimal toxicity when used alone. These results warrant further study in a Phase II trial.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Ohio</li></region></list><tree><country name="États-Unis"><region name="Ohio"><name sortKey="Plautz, Gregory E" sort="Plautz, Gregory E" uniqKey="Plautz G" first="Gregory E" last="Plautz">Gregory E. Plautz</name></region><name sortKey="Bukowski, Ronald M" sort="Bukowski, Ronald M" uniqKey="Bukowski R" first="Ronald M" last="Bukowski">Ronald M. Bukowski</name><name sortKey="Klein, Eric A" sort="Klein, Eric A" uniqKey="Klein E" first="Eric A" last="Klein">Eric A. Klein</name><name sortKey="Kursh, Elroy D" sort="Kursh, Elroy D" uniqKey="Kursh E" first="Elroy D" last="Kursh">Elroy D. Kursh</name><name sortKey="Novick, Andrew C" sort="Novick, Andrew C" uniqKey="Novick A" first="Andrew C" last="Novick">Andrew C. Novick</name><name sortKey="Olencki, Thomas E" sort="Olencki, Thomas E" uniqKey="Olencki T" first="Thomas E" last="Olencki">Thomas E. Olencki</name><name sortKey="Pienkny, Andrew" sort="Pienkny, Andrew" uniqKey="Pienkny A" first="Andrew" last="Pienkny">Andrew Pienkny</name><name sortKey="Sandstrom, Kate" sort="Sandstrom, Kate" uniqKey="Sandstrom K" first="Kate" last="Sandstrom">Kate Sandstrom</name><name sortKey="Shu, Suyu" sort="Shu, Suyu" uniqKey="Shu S" first="Suyu" last="Shu">Suyu Shu</name><name sortKey="Yetman, Randall J" sort="Yetman, Randall J" uniqKey="Yetman R" first="Randall J" last="Yetman">Randall J. Yetman</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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