Synthetic Poly(L-Glutamic Acid)-conjugated CpG Exhibits Antitumor Efficacy With Increased Retention in Tumor and Draining Lymph Nodes After Intratumoral Injection in a Mouse Model of Melanoma
There is an urgent need for new clinically applicable drug-delivery methods to enhance accumulation of immune-activating drugs in tumors. We synthesized a poly(L-glutamic acid)-CpG ODN2216 conjugate (PG-CpG) and injected it intratumorally into C57BL/6 mice bearing subcutaneous B16-ovalbumin melanoma. PG-CpG elicited the same potent antitumoral activity as CpG with respect to reducing tumor growth and triggering antigen-specific CD8+ T-cell responses in this well-established solid tumor model. Moreover, PG-CpG was retained significantly longer in both tumor and draining lymph nodes than was free CpG after intratumoral injec...
Source: Journal of Immunotherapy - December 3, 2016 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
The Characteristics of Naive-like T Cells in Tumor-infiltrating Lymphocytes From Human Lung Cancer
In this study, we show the characteristics of T-cell subsets in TILs isolated from NSCLC. CD3+ CD8+ CD45RA+ T cells outnumbered CD3+ CD4+ CD45RA+ T cells in CD45RA+ TILs, but it was the opposite in CD45RO+ TILs. Effector memory CD4+ T cells predominated in CD4+ TILs; about 10% of the stem cell-like memory T cells (Tscm) were detected in TILs. To further analyze their functions, we stimulated TILs from NSCLC patients by mitogens to examine cytokine production. Our data demonstrated that naive-phenotype T cells in TILs secret IFN-γ in abundance; TNF-α-producing T cells were significantly increased in TILs; there were more ...
Source: Journal of Immunotherapy - December 3, 2016 Category: Allergy & Immunology Tags: Basic Studies Source Type: research
Pembrolizumab-triggered Uveitis: An Additional Surrogate Marker for Responders in Melanoma Immunotherapy?
Immunotherapy leads to significantly prolonged survival of patients with metastatic melanoma. Autoimmune side effects including colitis, dermatitis, and endocrine abnormalities are common in patients treated with ipilimumab [anti-CTLA4 (cytotoxic T-lymphocyte-associated protein 4)]. Antibodies such as pembrolizumab that interfere with the PD-1 (programmed cell death 1)/PD-L1 pathway show greater efficacy and less toxicity than ipilimumab. Here we report 2 cases of pembrolizumab-induced uveitis associated with complete or partial tumor response. We suggest that uveitis may serve as a surrogate marker for a tumor response to...
Source: Journal of Immunotherapy - October 14, 2016 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Radiotherapy to Control Limited Melanoma Progression Following Ipilimumab
Durable local control of irradiated cancer and distant abscopal effects are presumably immune mediated. To evaluate the role of radiotherapy (RT) for limited progression after anti-CTLA4 checkpoint inhibition, medical records of all patients with surgically incurable stage III or IV melanoma from a single institution who received ipilimumab as first-line immunotherapy and subsequent RT were reviewed. Sixteen patients who received RT to all sites of limited melanoma progression were analyzed. Eight patients with an incomplete initial response to ipilimumab received RT to new or progressive disease, whereas the remaining 8 p...
Source: Journal of Immunotherapy - October 14, 2016 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Analysis of the Abscopal Effect With Anti-PD1 Therapy in Patients With Metastatic Solid Tumors
In conclusion, no patients with NSCLC or renal cancer showed abscopal effect, but 25% of patients with melanoma showed regression of nonirradiated lesions when anti-PD1 was continued after radiation to a tumor site that had progressed on anti-PD1 monotherapy. (Source: Journal of Immunotherapy)
Source: Journal of Immunotherapy - October 14, 2016 Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
