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Background AgenT-797 is a novel allogeneic iNKT cell therapy demonstrating activity in malignances and serious viral infections (i.e., SARS-CoV-2). In response to inflammatory injury, iNKTs home to critical organs, including lungs, dampen proinflammatory cytokines and protect epithelial tissues. INKTs drive response through activation of innate and adaptive immunity, recruitment/trans-activation of NK, B, and T cells, and myeloid cells via contact and soluble mediators. iNKTs represent a novel and attractive potential immunotherapy for viral ARDS. This analysis presents results from an ongoing phase 1/2 study of agenT-797 in mechanically ventilated patients with moderate to severe ARDS secondary to COVID- 19;NCT04582201. Methods As of February 2022, patients on mechanical ventilation with confirmed moderate to severe (Berlin Definition) ARDS, secondary to COVID-19 were treated with a single infusion of agenT-797 at 100, 300, or 1000 x 106 iNKT cells. Primary endpoint was safety and secondarily, time to extubation, prevention of secondary infections, persistence and alloimmunity were evaluated. Clinical benefit was defined as improvement/resolution of viral ARDS evaluated as time to extubation and survival at 30 days post-infusion. Results Twenty evaluable patients were treated with agenT-797 with a median age of 66 years (range 26-77;85% >=65y). Patients enrolled early in pandemic (pre-vaccines) and were heavily pre-treated with remdesivir, steroids and/or tocilizumab. No dose-limiting toxicities were observed. Tolerability was favorable with no cytokine release syndrome (CRS), neurotoxicity, or severe immune-related AEs. One SAE was deemed possibly related to agenT-797 (Dyspnea, Grade 4). The most frequent AEs deemed possibly related was pyrexia (grade 1;n=6). Survival was 70% (14/20) in this predominantly elderly, mechanically ventilated population. Early signals of reduction in ARDS symptoms, rapid extubation, and reduction in secondary infections were observed. AgenT-797 was detected in peripheral blood up to day 6 post-infusion, consistent with a rapid translocation from blood to tissue. Spikes in the blood during D1 and D2 showed a dose-proportional relationship, however, increased dose did not lead to prolonged peripheral persistence. Additional translational and biomarker evaluation is underway. Conclusions In patients with severe viral ARDS secondary to SARS-COV-2, agenT-797 demonstrated encouraging survival and disease mitigating benefit with a favorable tolerability profile. The deep and broad activity observed is likely attributed to iNKT cells' ability to promote viral clearance, home to the lungs, and reduce inflammation. These findings support the potential for a variant-agnostic therapy for patients with viral ARDS, a condition for which there are currently no effective therapies.
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Background We are developing MiNK-413;a novel allogeneic CAR-iNKT product targeting BCMA and secreting soluble IL-15 for treatment of relapsed/refractory Multiple Myeloma (rrMM). Chimeric Antigen Receptor (CAR)-T cell therapy has revolutionized treatment of rrMM with two autologous products already approved by the FDA. However, current treatments come with significant toxicity, cost, and logistical challenge and many patients relapse, with 60% of relapsed patients still expressing BCMA. To address these, we propose the use of invariant Natural Killer T (iNKT) cells as a platform for BCMA-targeted allogenic cell therapy for rrMM. iNKT cells have potent immunostimulatory activity and intrinsic CD1d-and NK receptor ligand targeted cytotoxicity, and do not cause Graft versus Host Disease due to their invariant T cell receptor. In our native iNKT cell (agenT-797) clinical trials for COVID, solid tumors and Multiple Myeloma we observe excellent tolerability to up to 1 billion cell dosing with minimal treatment-related adverse events, absence of signs of CRS or peripheral neuropathy, and early signs of biological activity. AgenT-797 is administered without prior lymphodepletion, which is an approach we intend to pursue with MiNK-413. Methods Our proprietary CARDISTM platform consists of highly diverse (>1010) scFv library screening followed by library-based direct functional selection in CAR format using mammalian display. Candidates can be further optimized using affinity tuning to ensure optimal and highly selective on-target/ on-tumor activity. We developed a manufacturing approach to engineer and specifically expand CAR and soluble IL-15-expressing allogeneic iNKT cells. Lead candidates are assessed in vitro and in vivo for cytotoxicity, cytokine secretion, exhaustion, tumor homing and persistence. Results Discovery using our CARDISTM platform generated a fully human, potent, and specific anti-BCMA CAR which forms the basis for MiNK-413. Xenograft in vivo studies demonstrate effective bone marrow homing, and potent cytotoxic activity, with soluble IL-15 prolonging persistence. In vitro data show potent immunomodulatory activity and lack of exhaustion against BCMA+ human hematologic tumor cell lines in vitro and in vivo. Conclusions Combination of our proprietary CARDISTM and iNKT platforms enabled rapid discovery and development of MiNK-413, a next generation armored allogeneic BCMA-targeting CAR therapies. MiNK-413 is eligible to target a broader rrMM patient population due to intrinsic iNKT cell properties such as effective bone-marrow homing, high BCMA specific activity augmented by natural CD1d and NK receptorligand mediated activity. We believe MiNK-413 will provide additional benefits to rrMM patients beyond currently available treatments.
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AIM: The impact of COVID-19 pandemic is pronounced in each healthcare process, including the management of breast cancer. The anxiety of COVID-19 changes patient preferences and some delay in routine controls and surgical managements occur. Some disintegration in medical care is to be expected during the pandemic, but the new coping strategies are needed in order to avoid delayed diagnosis of breast cancer. METHODS: A total number of 140 patients assigned for biopsy and diagnosed with breast cancer in our tertiary clinic between December 1st and August 31st were classified into 3 groups;A (December-February), B (March-May) and C (June-August) in order to compare the stage of breast cancer at the time of diagnosis before, during and after the peak period of pandemic. Clinical stage and age at presentation, family history of breast, ovarian and other types of cancer, BRCA (genetic testing), menopausal status, side of involvement (uni- or bilateral), histopathologic subtype, receptor positivity and molecular subtype were recorded for each patient. RESULTS: Group A included 20 stage I (27.77 %), 32 stage II (44.44 %), 16 stage III (22.22 %) and 4 stage IV (5.55 %) breast cancer patients. Group B had 5 stage I (22.72 %), 8 stage II (36.36 %), 7 stage III (31.81 %) and 2 stage IV (9.09 %) breast cancer patients. Whereas in group C there were 4 stage I (8.69 %), 21 stage II (45.65 %), 16 stage III (34.78 %) and 5 stage IV (10.86 %) patients with breast cancer. The number of late-stage cancer patients in group C was significantly higher in comparison with the other groups (p<0.05). CONCLUSION: We speculate that the change in incidence of breast cancer by stage is attributable to a delay in the diagnosis of breast cancer due to COVID-19 related restrictions and presentation of new cases at more advanced stages once the restrictions were eased. KEY WORDS: Biopsy, Breast cancer, COVID-19, PandemicStage.
ABSTRACT
AIM: The impact of COVID-19 pandemic is pronounced in each healthcare process, including the management of breast cancer. The anxiety of COVID-19 changes patient preferences and some delay in routine controls and surgical managements occur. Some disintegration in medical care is to be expected during the pandemic, but the new coping strategies are needed in order to avoid delayed diagnosis of breast cancer. METHODS: A total number of 140 patients assigned for biopsy and diagnosed with breast cancer in our tertiary clinic between December 1st and August 31st were classified into 3 groups;A (December-February), B (March-May) and C (June-August) in order to compare the stage of breast cancer at the time of diagnosis before, during and after the peak period of pandemic. Clinical stage and age at presentation, family history of breast, ovarian and other types of cancer, BRCA (genetic testing), menopausal status, side of involvement (uni- or bilateral), histopathologic subtype, receptor positivity and molecular subtype were recorded for each patient. RESULTS: Group A included 20 stage I (27.77 %), 32 stage II (44.44 %), 16 stage III (22.22 %) and 4 stage IV (5.55 %) breast cancer patients. Group B had 5 stage I (22.72 %), 8 stage II (36.36 %), 7 stage III (31.81 %) and 2 stage IV (9.09 %) breast cancer patients. Whereas in group C there were 4 stage I (8.69 %), 21 stage II (45.65 %), 16 stage III (34.78 %) and 5 stage IV (10.86 %) patients with breast cancer. The number of late-stage cancer patients in group C was significantly higher in comparison with the other groups (p<0.05). CONCLUSION: We speculate that the change in incidence of breast cancer by stage is attributable to a delay in the diagnosis of breast cancer due to COVID-19 related restrictions and presentation of new cases at more advanced stages once the restrictions were eased. KEY WORDS: Biopsy, Breast cancer, COVID-19, PandemicStage.
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The pandemic situation due to COVID-19 has crippled the lives of the whole world population and has affected almost every individual in one way or the other. Researchers have been intrigued due to the increasing number of strains and symptoms. Several approaches have been used to control the spread of this highly infectious disease: early detection of the infected individual, development of a suitable drug and containment of the spread of this virus. Although, several vaccines have been developed, they have shown to have their own limitations and side-effects. One of the measures which has been adopted by the global health agencies is to educate people (infected or uninfected) regarding the maintenance of strong immune system to prevent the infection and lessen the health complications. There are several important factors which determine the immunity of an individual. Eating balanced diet and maintaining the proper supplication of nutritional components are being suggested by health experts to keep the immunity strong. Minerals and vitamins must be maintained in the diet for proper health and immunity. Vitamins have various roles in human physiology. In this review, the relevance of vitamins in the maintenance of immunity has been discussed and reviewed in prevention of adverse health effects of COVID-19.
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AIM: The aim of this study is to point out the changes and possible delay in diagnosis or treatment of malignancies and an added risk of COVID-19 exposure emerging from these interventions, as well as to underline the increase of surgical demand once the pandemic measures are eased. METHODS: This study is a retrospective review of the patients operated between 11.03.2020 and 31.05.2020 in a center with a high incidence of COVID-19 infection during the pandemic. The numbers of emergency, elective and oncological surgeries as well as the increasing or decreasing trends of these interventions between March 11 and May 31 of previous years were compared with the corresponding period of 2020 or in other words the pandemic period. RESULTS: From March 11 to May 31, 2020 there was a progressive reduction in surgical activity, with only 195 operations: 61(31,28%) on a scheduled basis for tumor pathology, 59(30,25%) for benign pathology and 75(38,46%) for emergency indications. When the surgical trends of previous years are considered, all types of oncological surgeries decreased significantly in pandemic period March 11 to May 31, 2020. CONCLUSION: One of the most striking changes in medical care settings during the COVID-19 pandemic was observed in surgical management strategies. The most significant among these were the limitation of elective surgical procedures and the prioritization of emergency or non-delayed oncological operations. One may speculate that the standstill of elective surgeries including the oncological surgeries might have long term impacts on the clinical outcomes of patients as well as the healthcare workers and organizations. KEY WORDS: COVID-19, Emergency, Oncology, Pathology, SARS-CoV-2, Surgery. Lo scopo di questo studio è di evidenziare i cambiamenti e il possibile ritardo nella diagnosi o nel trattamento di tumori maligni e un ulteriore rischio di esposizione a COVID-19 che emerge da questi interventi, nonché di sottolineare l’aumento della domanda chirurgica una volta che le misure pandemiche saranno alleviate. Questo studio è una revisione retrospettiva dei pazienti operati tra l’11.03.2020 e il 31.05.2020 in un centro con un’alta incidenza di infezione da COVID-19 durante la pandemia. Il numero di interventi chirurgici di emergenza, elettivi e oncologici, nonché le tendenze crescenti o decrescenti di questi interventi tra l’11 marzo e il 31 maggio degli anni precedenti sono stati confrontati con il corrispondente periodo del 2020 cioè con il periodo di pandemia. Risultati: dall’11 marzo al 31 maggio 2020 si è verificata una progressiva riduzione dell’attività chirurgica, con solo 195 interventi: 61 (31,28%) su base programmata per patologia tumorale, 59 (30,25%) per patologia benigna e 75 (38,46%) per indicazioni di emergenza. Quando si considerano le tendenze chirurgiche degli anni precedenti, tutti i tipi di interventi chirurgici oncologici sono diminuiti significativamente nel periodo di pandemia dall’11 marzo al 31 maggio 2020. Conclusione: uno dei cambiamenti più sorprendenti nelle impostazioni di assistenza medica durante la pandemia di COVID-19 è stato osservato nelle strategie di gestione chirurgica. I più significativi tra questi sono stati la limitazione delle procedure chirurgiche elettive e la definizione delle priorità delle operazioni oncologiche di emergenza o non ritardate. Si potrebbe ipotizzare che l’arresto di interventi chirurgici opzionali, inclusi quelli oncologici, potrebbe avere impatti a lungo termine sugli esiti clinici dei pazienti, nonché degli operatori sanitari e delle organizzazioni.
ABSTRACT
AIM: The aim of this study is to point out the changes and possible delay in diagnosis or treatment of malignancies and an added risk of COVID-19 exposure emerging from these interventions, as well as to underline the increase of surgical demand once the pandemic measures are eased. METHODS: This study is a retrospective review of the patients operated between 11.03.2020 and 31.05.2020 in a center with a high incidence of COVID-19 infection during the pandemic. The numbers of emergency, elective and oncological surgeries as well as the increasing or decreasing trends of these interventions between March 11 and May 31 of previous years were compared with the corresponding period of 2020 or in other words the pandemic period. RESULTS: From March 11 to May 31, 2020 there was a progressive reduction in surgical activity, with only 195 operations: 61(31,28%) on a scheduled basis for tumor pathology, 59(30,25%) for benign pathology and 75(38,46%) for emergency indications. When the surgical trends of previous years are considered, all types of oncological surgeries decreased significantly in pandemic period March 11 to May 31, 2020. CONCLUSION: One of the most striking changes in medical care settings during the COVID-19 pandemic was observed in surgical management strategies. The most significant among these were the limitation of elective surgical procedures and the prioritization of emergency or non-delayed oncological operations. One may speculate that the standstill of elective surgeries including the oncological surgeries might have long term impacts on the clinical outcomes of patients as well as the healthcare workers and organizations. KEY WORDS: COVID-19, Emergency, Oncology, Pathology, SARS-CoV-2, Surgery.
ABSTRACT
AIM: The aim of this study is to point out the changes and possible delay in diagnosis or treatment of malignancies and an added risk of COVID-19 exposure emerging from these interventions, as well as to underline the increase of surgical demand once the pandemic measures are eased. METHODS: This study is a retrospective review of the patients operated between 11.03.2020 and 31.05.2020 in a center with a high incidence of COVID-19 infection during the pandemic. The numbers of emergency, elective and oncological surgeries as well as the increasing or decreasing trends of these interventions between March 11 and May 31 of previous years were compared with the corresponding period of 2020 or in other words the pandemic period. RESULTS: From March 11 to May 31, 2020 there was a progressive reduction in surgical activity, with only 195 operations: 61(31,28%) on a scheduled basis for tumor pathology, 59(30,25%) for benign pathology and 75(38,46%) for emergency indications. When the surgical trends of previous years are considered, all types of oncological surgeries decreased significantly in pandemic period March 11 to May 31, 2020. CONCLUSION: One of the most striking changes in medical care settings during the COVID-19 pandemic was observed in surgical management strategies. The most significant among these were the limitation of elective surgical procedures and the prioritization of emergency or non-delayed oncological operations. One may speculate that the standstill of elective surgeries including the oncological surgeries might have long term impacts on the clinical outcomes of patients as well as the healthcare workers and organizations. KEY WORDS: COVID-19, Emergency, Oncology, Pathology, SARS-CoV-2, Surgery.