Publications by authors named "Howard Kaufman"
Article Synopsis
- * The study focused on JEN-101, a localized injection of interleukin-12 designed to boost immune response in dogs with advanced melanoma, evaluating its safety, effectiveness, and immune effects over several doses.
- * Results indicated that JEN-101 was well-tolerated with manageable side effects, and it showed promising biological responses, suggesting its potential for further research and relevance to human cancer treatment.
Background: First-line treatment with pembrolizumab plus chemotherapy in recurrent and metastatic head and neck squamous cell carcinomas (HNSCC) has improved survival. However, the overall response rate with this standard of care regimen (SOC) remains limited. Interleukin (IL)-12 is a potent cytokine that facilitates the crosstalk between innate and adaptive immunity, making it crucial in the antitumor response.
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- - Talimogene laherparapvec (T-VEC) is an innovative treatment made from a modified herpes virus, approved for hard-to-treat melanoma, and this study examines genetic factors that might predict treatment success in patients.
- - The analysis included data from 93 melanoma patients treated with T-VEC, with 30% showing complete tumor regression; key factors linked to better outcomes included early-stage disease and lack of certain metastases.
- - Among 54 patients with available genetic data, most had gene mutations, and a specific mutation (TERT promoter) was notably linked to better clinical responses, suggesting it could influence treatment effectiveness.
Article Synopsis
- Image-guided cryoablation is a treatment for cancer that freezes tumors to help fight them.
- Researchers believed that this treatment could help the immune system work better against stubborn tumors that didn't respond to other therapies.
- In a study with 17 patients, cryoablation was found to be safe and helped improve tumor responses in some patients, showing promise for this combined treatment approach.
Article Synopsis
- * Talimogene laherparepvec is an engineered herpes virus that delivers the human cytokine GM-CSF directly to recurrent melanoma tumors, enhancing antitumor immunity.
- * The review discusses various cytokines and chemokines that could improve the effectiveness of oncolytic viruses in cancer therapy, emphasizing the need for a better understanding of their delivery mechanisms to maximize patient outcomes.
Article Synopsis
- Merkel cell carcinoma (MCC) is an aggressive cancer with bad outcomes, and the study focused on the potential of a blood test (AMERK) to predict patient survival based on the presence of antibodies against Merkel cell polyomavirus.
- In a study of 261 patients, nearly half were seropositive, and results showed that those with positive AMERK tests had significantly better survival rates, particularly in patients with localized disease.
- The findings suggest that measuring MCPyV antibodies could help personalize treatments and improve risk assessment for MCC patients, though the study has limitations due to its retrospective nature.
Background: Current guidelines for management of anorectal abscesses make no recommendations for operative vs bedside incision and drainage (I&D). The purpose of this study was to determine if management in the operating room is necessary to adequately drain anorectal abscesses and prevent short-term complications for patients presenting to the emergency department (ED).
Methods: Patients with perirectal abscesses were identified and divided into two groups based on intervention type: "bedside" or "operative.
Article Synopsis
- Scientists believe that delivering special medicines directly into tumors could help fight cancer better.
- An expert group worked together to figure out how to create better tests for these new treatments, including which patients to help.
- They discussed different ideas on how to design these tests, so they can learn the most about how well the new therapies work for different types of cancer.
Article Synopsis
- Glioblastoma (GBM) is a deadly brain tumor with limited treatment options, primarily driven by a subpopulation of cancer stem-like cells that resist therapies.
- Oncolytic herpes simplex virus (oHSV), particularly talimogene laherparepvec, has shown promise in targeting cancer cells and inducing immune responses, yet its application in GBM remains under-explored.
- A new approach using G47Δ-mIL2, an oHSV designed to locally express interleukin 2 (IL-2), was found to improve survival in mouse GBM models without causing the systemic side effects typically associated with IL-2 treatment.
Article Synopsis
- IL-12 is a powerful cytokine that enhances both innate and adaptive immune responses against cancer, but its use has been limited due to toxicity from systemic delivery.
- The development of an anchored variant called ANK-101 allows for intratumoral (i.t.) administration, which creates a stable drug depot in tumors, leading to longer retention and greater therapeutic effects compared to unanchored IL-12.
- ANK-101 has shown significant antitumor activity in various mouse models, even in cases resistant to other therapies, and demonstrated good tolerance in macaques, suggesting it has strong potential for clinical use.
Article Synopsis
- * Despite its benefits, IL-2 therapy has downsides, such as a short lifespan in the bloodstream, poor targeting of tumors, and serious side effects at high doses.
- * Oncolytic viruses (OVs) can enhance cancer immunotherapy by safely delivering IL-2 directly to tumors, and combining IL-2 with OVs has shown promising results in preclinical and clinical studies for improving antitumor responses.
Article Synopsis
- Recent research is shifting cancer treatment focus from direct viral effects to immune activation, utilizing oncotropic viruses like PV001-DV, a safe strain of Dengue virus known for its immune-boosting properties.
- The study demonstrated PV001-DV's ability to directly kill melanoma cells and enhance immune responses in patient blood cells, showing promising results in tumor cell death.
- These findings support further clinical trials of PV001-DV in advanced melanoma patients who have not responded to other treatments.
Article Synopsis
- Immunotherapies are increasingly used as primary treatments for advanced cancers, and this study explores how combining oncolytic virus (OV) and radiation therapy (RT) might enhance treatment outcomes.
- The research used mouse and human cancer cell lines, along with a skin cancer mouse model, showing that the combination therapy not only reduces tumor growth but also transforms 'cold' tumors into 'hot' tumors, which are more responsive to immune attacks.
- A patient with cutaneous squamous cell carcinoma experienced significant improvement after receiving the combined treatment, remaining free of disease progression for over 44 months, suggesting that the combination of OV, RT, and immune checkpoint inhibitors (ICIs) could be beneficial for patients with refractory cancers.
Article Synopsis
- Combining immune checkpoint inhibitors (ICIs) with talimogene laherparepvec (TVEC) may enhance antitumor responses, but the risk of skin-related immune adverse events (cirAEs) with this combination hasn't been previously studied.
- In a study comparing patients treated with ICI alone versus those treated with both ICI and TVEC, it was discovered that the combination therapy resulted in a higher incidence of cirAEs, with a 2-fold increased risk for those on ICI + TVEC.
- The study's retrospective design and limited sample size highlight the need for careful monitoring of patients on combination therapies, pointing to potential improvements in how dermatologists and oncologists provide counseling.
Article Synopsis
- - The study analyzed 145 patients with regionally metastatic cutaneous squamous cell carcinoma (cSCC) who underwent parotidectomy and neck dissection, focusing on their overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) over three years.
- - Results showed that the overall survival rate was 74.5%, while the disease-specific survival and disease-free survival rates were 85.5% and 64.8%, respectively; factors like immune status and lymphovascular invasion significantly affected these outcomes.
- - The findings indicate that patients with immunosuppression and lymphovascular invasion had worse survival outcomes; additionally, those with positive surgical margins or fewer than 18 lymph nodes
Article Synopsis
- High-dose interleukin-2 (HD IL-2) and pembrolizumab are FDA-approved treatments for metastatic melanoma, and this study aims to evaluate their combined safety.
- In a Phase Ib trial, 10 patients received differing doses of IL-2 alongside pembrolizumab to determine the maximum tolerated dose (MTD).
- Results showed that adverse events increased with higher IL-2 doses, but no serious toxicities were found, and one patient experienced a partial response, suggesting the combination is manageable and warrants further exploration.
Article Synopsis
- * T-VEC is the only widely approved OV therapy, specifically used for treating recurrent melanoma, with approval dating back to 2015 and a growing body of clinical data supporting its efficacy.
- * The review emphasizes the need for better understanding the biology of OVs to maximize their therapeutic potential and discusses the challenges faced in the development of novel OVs, including clinical and regulatory issues.
Article Synopsis
- The CAPRA trial evaluated the combination of Coxsackievirus A21 (V937) and pembrolizumab for treating advanced melanoma, focusing on safety as the primary outcome.
- In this study, 36 patients were treated, with a 47% objective response rate, including a 22% complete response rate, and 82% of responders maintaining their response for over 6 months.
- Notably, the trial found that tumor microenvironments in responders had lower CD3CD8 T cell density than nonresponders, indicating potential effectiveness even in less immunologically active tumors.
Article Synopsis
- Gene therapy presents various innovative strategies, such as gene replacement therapy, cancer vaccines, oncolytic viruses, cellular therapy, and gene editing, for treating cancer.
- Understanding these modalities is crucial for effectively managing patients with cancer.
- The review emphasizes the critical role surgeons play in diagnosing and treating cancer, highlighting the need for them to be informed about gene therapy to enhance patient outcomes.
Article Synopsis
- - The study explored the effectiveness of cemiplimab as a neoadjuvant therapy for patients with resectable cutaneous squamous-cell carcinoma, aiming to determine its impact on achieving a pathological complete response before surgery.
- - Out of 79 participants, 51% achieved a pathological complete response, while 68% showed a positive response on imaging; these outcomes suggest cemiplimab is effective for this patient group.
- - However, 87% of patients experienced adverse events, highlighting the need for careful monitoring and further research to balance treatment benefits with potential side effects.
Article Synopsis
- Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer linked to UV exposure and the Merkel cell polyoma virus, with increasing incidence and high recurrence/mortality rates.
- Immune checkpoint inhibitors like avelumab and pembrolizumab show promise in treating advanced MCC, but nearly 50% of patients do not respond effectively.
- A study on the combination treatment of ipilimumab and nivolumab in patients with refractory MCC found limited effectiveness, with only 23% achieving stable disease and a median overall survival of just 4.7 months.
Article Synopsis
- Systemic dosing of cytokines and agonist antibodies for cancer treatment is limited by on-target, off-tumor toxicity, prompting the exploration of intratumoral administration as a solution.
- The text focuses on strategies to retain immune agonists within tumors, suggesting the use of extracellular matrix components, cell surface receptor targets, or particulate materials to prevent rapid drug diffusion out of the tumor.
- Effective tissue retention for intratumoral therapy is crucial to maximize drug exposure to the tumor while reducing systemic toxicity, emphasizing the need for matched drug release kinetics and receptor-mediated uptake.
Talimogene Laherparepvec: Moving From First-In-Class to Best-In-Class.
Front Mol Biosci
February 2022
Article Synopsis
- Talimogene laherparepvec (T-VEC) is a modified herpes simplex virus designed to treat melanoma by selectively targeting cancer cells and boosting the immune response through GM-CSF.
- Approved by the FDA in 2015, T-VEC is specifically for patients with recurrent melanoma after initial surgery and represents the first oncolytic virus to receive such approval.
- The review highlights the ongoing research for T-VEC’s effectiveness in non-melanoma cancers, clinical trial outcomes, identifying biomarkers for patient response, and future research directions to maximize the benefits of oncolytic virus therapies.