Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Publication year range
1.
J Transl Med ; 8: 71, 2010 Jul 23.
Article in English | MEDLINE | ID: mdl-20653948

ABSTRACT

BACKGROUND: IMP321 is a recombinant soluble LAG-3Ig fusion protein that binds to MHC class II with high avidity and mediates APC and then antigen-experienced memory CD8+ T cell activation. We report clinical and biological results of a phase I/II in patients with metastatic breast carcinoma (MBC) receiving first-line paclitaxel weekly, 3 weeks out of 4. METHODS: MBC patients were administered one dose of IMP321 s.c. every two weeks for a total of 24 weeks (12 injections). The repeated single doses were administered the day after chemotherapy at D2 and D16 of the 28-day cycles of paclitaxel (80 mg/m2 at D1, D8 and D15, for 6 cycles). Blood samples were taken 13 days after the sixth and the twelfth IMP321 injections to determine sustained APC, NK and memory CD8 T cell responses. RESULTS: Thirty MBC patients received IMP321 in three cohorts (doses: 0.25, 1.25 and 6.25 mg). IMP321 induced both a sustained increase in the number and activation of APC (monocytes and dendritic cells) and an increase in the percentage of NK and long-lived cytotoxic effector-memory CD8 T cells. Clinical benefit was observed for 90% of patients with only 3 progressors at 6 months. Also, the objective tumor response rate of 50% compared favorably to the 25% rate reported in the historical control group. CONCLUSIONS: The absence of toxicity and the demonstration of activity strongly support the future development of this agent for clinical use in combined first-line regimens. TRIAL REGISTRATION: ClinicalTrials.gov NCT00349934.


Subject(s)
Antigens, CD/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/immunology , Immunity/immunology , Immunotherapy , Paclitaxel/therapeutic use , Aged , Antibodies, Neoplasm/immunology , Antigens, CD/adverse effects , Antigens, CD/immunology , Antigens, CD/pharmacology , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Breast Neoplasms/pathology , Cell Count , Drug Administration Schedule , Female , Humans , Lymphocyte Activation/drug effects , Lymphocyte Activation/immunology , Middle Aged , Monocytes/cytology , Monocytes/drug effects , Neoplasm Metastasis , Paclitaxel/adverse effects , Paclitaxel/pharmacology , Remission Induction , Treatment Outcome , Lymphocyte Activation Gene 3 Protein
2.
Bull Cancer ; 94(7 Suppl): F69-76, 2007 Jul.
Article in French | MEDLINE | ID: mdl-17845996

ABSTRACT

Therapeutic vaccines for prostate cancer were initially reported as limited with low immunological responses and uncertain clinical benefit. Recently, new methods become available, such preparations of well-characterized autologous dendritic cells, and use of gene therapy tools to increase whole-tumor cells or host tissue immunogenicity. These are able to enhance and diversify therapeutic options. Indeed, several vaccinal approaches are being investigated, including optimized mature dendritic cells, allogeneic genetically modified tumor cells, or viral vectors. Due to the description of immunological and clinical responses, large phase III randomized trials are now conducted. After summarizing the mechanistic basis for these approaches, this review describes the experience with the most recent and promising clinical studies and introduces short-term perspectives that could lead to improvement in healthcare offer for prostate cancer patients.


Subject(s)
Cancer Vaccines/therapeutic use , Dendritic Cells/transplantation , Immunotherapy/methods , Prostatic Neoplasms/therapy , Dendritic Cells/immunology , Genetic Therapy , Humans , Male , Prostate-Specific Antigen/immunology , Prostatic Neoplasms/immunology , Transfection/methods , Transplantation, Homologous
SELECTION OF CITATIONS
SEARCH DETAIL
...