76 research outputs found
Melanoma vaccines
No full textMany vaccines have been very successful. They can protect from many different infectious diseases, and thus contribute enormously to public health. The majority of successful vaccines induce neutralizing antibodies, which are essential for protection from disease, by the inhibition of microbe invasion and spread through the body, via extracellular compartments, or by neutralization of toxins. In contrast to infectious diseases, the pathological process in cancer is primarily intracellular. Immunity to cancer depends mainly on T cells which are capable of identifying and eliminating abnormal cells, via recognition of peptide antigens presented by major histocompatibility complex molecules at the cell surface. In some instances, tumor-specific antibodies can contribute to immune defense against cancer. Unfortunately, for many solid tumors (including melanoma), this mechanism is insufficient. Nevertheless, the search for cancer-neutralizing antibodies continues, similar to, e.g., HIV neutralizing antibodies. In this chapter, we focus on the development of T cell vaccines, a great challenge but also a promising approach as a new therapy for melanoma, other cancers, and intracellular pathogen
Phase I/Ib clinical trial of Sabatolimab, an Anti-TIM-3 Antibody, Alone and in Combination With Spartalizumab, an Anti-PD-1 Antibody, in Advanced Solid Tumors
No full textPurpose: Sabatolimab (MBG453) and spartalizumab are monoclonal antibodies that bind T-cell immunoglobulin domain and mucin domain-3 (TIM-3) and programed death-1 (PD-1), respectively. This phase I/II study evaluated the safety and efficacy of sabatolimab, with or without spartalizumab, in patients with advanced solid tumors.
Experimental design: Primary objectives of the phase I/Ib part were to characterize the safety and estimate recommended doses for future studies (RP2Ds). Dose escalation was guided by a Bayesian (hierarchical) logistic regression model. Sabatolimab was administered intravenously, 20-1200 mg, every 2 or 4 weeks (Q2W, Q4W). Spartalizumab was administered intravenously, 80-400 mg, Q2W or Q4W.
Results: Enrolled patients (n=219) had a range of cancers, most commonly ovarian (17%) and colorectal cancer (7%); patients received sabatolimab (n=133) or sabatolimab plus spartalizumab (n=86). The maximum tolerated dose was not reached. The most common adverse event suspected to be treatment-related was fatigue (9%, sabatolimab; 15%, combination). No responses were seen with sabatolimab. Five patients receiving combination treatment had partial responses (6%; lasting 12-27 months), in colorectal cancer (n=2), non-small cell lung cancer (NSCLC), malignant perianal melanoma, and SCLC. Of the five, two patients had elevated expression of immune markers in baseline biopsies; another three had >10% TIM-3 positive staining, including one patient with NSCLC who received prior PD-1 therapy.
Conclusions: Sabatolimab plus spartalizumab was well tolerated and showed preliminary signs of antitumor activity. The RP2D for sabatolimab was selected as 800 mg Q4W (alternatively Q3W or Q2W schedules, based on modeling), with or without 400 mg spartalizumab Q4W
P2.07-002 Drug-Related Pneumonitis in Advanced Non-Small-Cell Lung Cancer (NSCLC) Patients Treated with Commercial PD-1 Inhibitors
No full textP1.01-055 Spectrum of Early Progression in Advanced NSCLC Patients Treated with PD-1 Inhibitors: Identifying Markers for Poor Outcome
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Regional Lymph Node Basin (RLNB) Relapse after Adjuvant Ipilimumab (Ipi) Anti-CTLA4 Immunotherapy in Stage III Melanoma: A Subgroup Analysis of a Randomized Placebo-Controlled Trial
No full textGeneration of Functional CLL-Specific Cord Blood CTL Using CD40-Ligated CLL APC
No full textPMCID: PMC3526610This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Long-Term Safety and Clinical Outcomes of Atezolizumab in Head and Neck Cancer: Phase Ia Trial Results
No full text9306 ORAL Safety and Efficacy of Ipilimumab-treated Patients With Melanoma and Brain Metastases
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