PURPOSE: Listeria monocytogenes (Lm)-based vaccines stimulate both innate and adaptive immunity. ANZ-100 is a live-attenuated Lm strain (Lm ΔactA/ΔinlB). Uptake by phagocytes in the liver results in local inflammatory responses and activation and recruitment of natural killer (NK) and T cells, in association with increased survival of mice bearing hepatic metastases. The Lm ΔactA/ΔinlB strain, engineered to express human mesothelin (CRS-207), a tumor-associated antigen expressed by a variety of tumors, induces mesothelin-specific T-cell responses against mesothelin-expressing murine tumors. These two phase I studies test ANZ-100 and CRS-207 in subjects with liver metastases and mesothelin-expressing cancers, respectively. EXPERIMENTAL DESIGN: A single intravenous injection of ANZ-100 was evaluated in a dose escalation study in subjects with liver metastases. Nine subjects received 1 × 10(6), 3 × 10(7), or 3 × 10(8) colony-forming units (cfu). CRS-207 was evaluated in a dose-escalation study in subjects with mesothelioma, lung, pancreatic, or ovarian cancers. Seventeen subjects received up to 4 doses of 1 × 10(8), 3 × 10(8), 1 × 10(9), or 1 × 10(10) cfu. RESULTS: A single infusion of ANZ-100 was well tolerated to the maximum planned dose. Adverse events included transient laboratory abnormalities and symptoms associated with cytokine release. Multiple infusions of CRS-207 were well tolerated up to 1 × 10(9) cfu, the determined maximum tolerated dose. Immune activation was observed for both ANZ-100 and CRS-207 as measured by serum cytokine/chemokine levels and NK cell activation. In the CRS-207 study, listeriolysin O and mesothelin-specific T-cell responses were detected and 37% of subjects lived ≥15 months. CONCLUSIONS: ANZ-100 and CRS-207 administration was safe and resulted in immune activation.
PURPOSE:Listeria monocytogenes (Lm)-based vaccines stimulate both innate and adaptive immunity. ANZ-100 is a live-attenuated Lm strain (Lm ΔactA/ΔinlB). Uptake by phagocytes in the liver results in local inflammatory responses and activation and recruitment of natural killer (NK) and T cells, in association with increased survival of mice bearing hepatic metastases. The Lm ΔactA/ΔinlB strain, engineered to express humanmesothelin (CRS-207), a tumor-associated antigen expressed by a variety of tumors, induces mesothelin-specific T-cell responses against mesothelin-expressing murinetumors. These two phase I studies test ANZ-100 and CRS-207 in subjects with liver metastases and mesothelin-expressing cancers, respectively. EXPERIMENTAL DESIGN: A single intravenous injection of ANZ-100 was evaluated in a dose escalation study in subjects with liver metastases. Nine subjects received 1 × 10(6), 3 × 10(7), or 3 × 10(8) colony-forming units (cfu). CRS-207 was evaluated in a dose-escalation study in subjects with mesothelioma, lung, pancreatic, or ovarian cancers. Seventeen subjects received up to 4 doses of 1 × 10(8), 3 × 10(8), 1 × 10(9), or 1 × 10(10) cfu. RESULTS: A single infusion of ANZ-100 was well tolerated to the maximum planned dose. Adverse events included transient laboratory abnormalities and symptoms associated with cytokine release. Multiple infusions of CRS-207 were well tolerated up to 1 × 10(9) cfu, the determined maximum tolerated dose. Immune activation was observed for both ANZ-100 and CRS-207 as measured by serum cytokine/chemokine levels and NK cell activation. In the CRS-207 study, listeriolysin O and mesothelin-specific T-cell responses were detected and 37% of subjects lived ≥15 months. CONCLUSIONS:ANZ-100 and CRS-207 administration was safe and resulted in immune activation.
Authors: H T Maecker; H S Dunn; M A Suni; E Khatamzas; C J Pitcher; T Bunde; N Persaud; W Trigona; T M Fu; E Sinclair; B M Bredt; J M McCune; V C Maino; F Kern; L J Picker Journal: J Immunol Methods Date: 2001-09-01 Impact factor: 2.303
Authors: Jeffrey R Currier; Ellen G Kuta; Ellen Turk; Lyndsay B Earhart; Larry Loomis-Price; Sylvia Janetzki; Guido Ferrari; Deborah L Birx; Josephine H Cox Journal: J Immunol Methods Date: 2002-02-01 Impact factor: 2.303
Authors: E M Jaffee; R H Hruban; B Biedrzycki; D Laheru; K Schepers; P R Sauter; M Goemann; J Coleman; L Grochow; R C Donehower; K D Lillemoe; S O'Reilly; R A Abrams; D M Pardoll; J L Cameron; C J Yeo Journal: J Clin Oncol Date: 2001-01-01 Impact factor: 44.544
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Authors: Amy Morck Thomas; Lynn M Santarsiero; Eric R Lutz; Todd D Armstrong; Yi-Cheng Chen; Lan-Qing Huang; Daniel A Laheru; Michael Goggins; Ralph H Hruban; Elizabeth M Jaffee Journal: J Exp Med Date: 2004-08-02 Impact factor: 14.307
Authors: Sherrill L Macura; Jedd M Hillegass; Jeremy L Steinbacher; Maximilian B MacPherson; Arti Shukla; Stacie L Beuschel; Timothy N Perkins; Kelly J Butnor; Melissa J Lathrop; Mutlay Sayan; Khan Hekmatyar; Douglas J Taatjes; Risto A Kauppinen; Christopher C Landry; Brooke T Mossman Journal: J Histochem Cytochem Date: 2012-06-21 Impact factor: 2.479