The new generation of cancer immunotherapy ISAC is here: the tumor is completely regressed, clinical trials are in progress

Over the past 15 years, immunotherapy, represented by checkpoint inhibitors, has led to significant changes in cancer treatment, but the effectiveness of such therapies remains limited.
for example, most patients treated with PD-1/L1 inhibitors did not receive complete remission, and only a few patients had a persistent subsidion of the tumor after treatment.
Toll-like subject (TLR) agonist activates antigen delivery cells (APC) and enhances T-cell immunity to new tumor antigens.
can improve the anti-tumor activity of immuno-checkpoint inhibitors by combining with these congenic immunostidants.
, however, the systemic administration of TLR agitants often triggers toxic reactions, and intraculsive injections, while improving the drug's tolerance, are also limited by factors such as tumor size in practice.
in a new study published December 7 in Nature Cancer, researchers from Bolt Biotherapeutics and Stanford University School of Medicine developed an immunostature antibody concedes (ISAC) that combines the accuracy of antibody-targeted tumors with the lethal potential of congenital and adaptive immune systems into a single drug, enabling complete tumor recedation and long-lasting anti-tumor immunity in a variety of tumor models.
ISAC is made up of a single anti-tumor target that is coupled with an immunoexcitant through a non-lysable joint (linker).
this study, researchers designed to combine lyxident resistance to produce T785-ISAC by combining linker with TLR7/8 astrations (T785), and the immune stimulation potential of T785-ISAC is not limited to lysoxi monoantigen.
in-body experiments, lytoxides monoantigen TLR7/8 ISAC activates antigen delivery cells (APC) and induces their maturation.
APC activation depends on the functional Fc fragments of TLR astrists and antibodies.
shows the importance of Fc-R during the absorption and internalization of ISAC.
ISAC induces APC activation through the joint action of Fc-R and TLR, and the synergy of the two signaling paths provides ISAC with the ability to enhance the function of anti-tumor myelin cells.
To determine whether the co-priced connection between T785 and monoantigen enlarges the body's anti-tumor immunity, in the her2 expression heterogeneity transplant model of curtojudan anti-drug, the researchers found that curto-pearl single-anti-T785-ISAC systemic drugation was effective in controlling tumor growth.
, ISAC induces a strong inflammatory environment, resulting in increased active myelin APC accumulation, local cytokines, and coercion factors.
the researchers then assessed the efficacy of ISAC in large, anti-treatable tumors (about 500mm3) in the presence of B, T and NK cells.
mice expressing rheher2 were cured after receiving the T785-ISAC therapy that targeted HER2, the tumor subsided completely, and the cured mice were further protected when the tumor was re-implanted.
researchers tested CL264-ISAC, a TLR7-specific astrogen.
results show that CL264-ISAC is more effective than T785-ISAC in inducing activated and anti-tumor activity in myelin-like APC, which confirms that the efficacy of TLR agonists affects the efficacy of ISAC.
, however, CL264-ISAC causes systemic cytokine secretion and short-term weight loss, suggesting possible therapeutic toxicity.
another possible limitation of ISAC is the production of anti-drug antibodies (anti-drug antibody), which may promote the production of anti-drug antibodies and affect the efficacy of the drug.
, new ISAC therapies have strong preclinical anti-tumor activity, and these results provide a strong basis for the clinical development of ISAC.
that the ISAC drug BDC-1001 presented in this study is being clinically I./II. in patients with HER2 expression tumors.
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