On-target restoration of a split T cell-engaging antibody for precision immunotherapy

T cell-engaging immunotherapies are changing the landscape of current cancer care. However, suitable target antigens are scarce, restricting these strategies to very few tumor types. Here, we report on a T cell-engaging antibody derivative that comes in two complementary halves and addresses antigen combinations instead of single molecules. Each half, now coined hemibody, contains an antigen-specific single-chain variable fragment (scFv) fused to either the variable light (V-L) or variable heavy (V-H) chain domain of an anti-CD3 antibody. When the two hemibodies simultaneously bind their respective antigens on a single cell, they align and reconstitute the original CD3-binding site to engage T cells. Employing preclinical models for aggressive leukemia and breast cancer, we show that by the combinatorial nature of this approach, T lymphocytes exclusively eliminate dual antigen-positive cells while sparing single positive bystanders. This allows for precision targeting of cancers not amenable to current immunotherapies

PENGARUH ATOPI TERHADAP TIMBULNYA DERMATITIS KONTAK PADA MAHASISWIRNPENDIDIKAN DOKTER FAKULTAS KEDOKTERAN UNIVERSITAS SYIAH KUALA RNBANDA ACEH

Dermatitis kontak adalah inflamasi non infeksi pada kulit yang disebabkan karena pemaparan dengan suatu zat tertentu yang dapat mengiritasi kulit atau menyebabkan reaksi alergi. Perempuan lebih sering mengalami dermatitis kontak dibandingkan laki-laki. Atopi merupakan salah satu faktor predisposisi timbulnya dermatitis kontak. Penelitian ini bertujuan untuk mengetahui pengaruh atopi terhadap timbulnya dermatitis kontak pada mahasiswi Pendidikan Dokter Fakultas Kedokteran Universitas Syiah Kuala Banda Aceh. Penelitian ini bersifat analitik dengan pendekatan cross sectional. Data yang digunakan adalah data primer yang diperoleh dengan wawancara langsung pada responden. Uji statistik dengan menggunakan Chi Square diperoleh nilai p yang signifikan sebesar 0,00, ini berarti p < 0,05 maka secara statistik didapatkan hubungan antara atopi dengan dermatitis kontak dengan rasio prevalensi 2,17, artinya seseorang yang menderita atopi memiliki peluang sebesar 2,17 kali untuk mengalami dermatitis kontak dibandingkan dengan orang yang tidak menderita atopi. Bahan yang paling sering menyebabkan dermatitis kontak pada mahasiswi adalah deterjen dan kosmetik. Hasil penelitian yang diperoleh ada pengaruh atopi terhadap timbulnya dermatitis kontak pada mahasiswi Pendidikan Dokter FK Unsyiah Banda Aceh, dimana mahasiswi yang menderita atopi cenderung mengalami dermatitis kontak.Kata kunci: Atopi, Dermatitis kontak Alergi, Dermatitis kontak iritanBanda Ace

Variant signaling topology at the cancer cell–T-cell interface induced by a two-component T-cell engager

No abstract available

Long-term survival of patients with CLL after allogeneic transplantation: A report from the European Society for Blood and Marrow Transplantation

Even with the availability of targeted drugs, allogeneic hematopoietic cell transplantation (allo-HCT) is the only therapy with curative potential for patients with CLL. Cure can be assessed by comparing long-term survival of patients to the matched general population. Using data from 2589 patients who received allo-HCT between 2000 and 2010, we used landmark analyses and methods from relative survival analysis to calculate excess mortality compared with an age-, sex- and calendar year-matched general population. Estimated event-free survival, overall survival and non-relapse mortality (NRM) 10 years after allo-HCT were 28% (95% confidence interval (CI), 25-31), 35% (95% CI, 32-38) and 40% (95% CI, 37-42), respectively. Patients who passed the 5-year landmark event-free survival (N=394) had a 79% probability (95% CI, 73-85) of surviving the subsequent 5 years without an event. Relapse and NRM contributed equally to treatment failure. Five-year mortality for 45- and 65-year-old reference patients who were event-free at the 5-year landmark was 8% and 47% compared with 3% and 14% in the matched general population, respectively. The prospect of long-term disease-free survival remains an argument to consider allo-HCT for young patients with high-risk CLL, and programs to understand and prevent late causes of failure for long-term survivors are warranted, especially for older patients