Oncology

Atrimer™ therapeutics in oncology: Exploiting the Atrimer advantage


Atrimer
drug candidates that act as receptor activators may provide an important addition to the current arsenal of anti-cancer therapies. The trivalent binding domains of Atrimers are especially suited to activating receptors that mediate apoptosis, or programmed cell death. This trivalent specificity applies as well to stimulating immune cells involved in natural defenses against cancer.

What is more, when the therapeutic strategy calls for drug conjugates, the Atrimer structure is uniquely disposed to facilitate the attachment of various anti-cancer agents for guided transport to target tumors.

Atrimer™ activators: Inducing cancer-cell death

Image: In a therapeutic strategy to kill cancer cells, Atrimers engage the DR4 receptor to trigger programmed cell death, or apoptosis. These Atrimers effectively mimic the activity of a natural molecule, TRAIL, which also activates death receptors. In contrast to the native TRAIL ligand, however, the Atrimers do not bind to decoy receptors that dampen apoptosis.

In a therapeutic strategy to kill cancer cells, Atrimer drug candidates engage the DR4 receptor to trigger programmed cell death, or apoptosis. These drug candidates effectively mimic the activity of a natural molecule, TRAIL, which also activates death receptors. In contrast to the native TRAIL ligand, however, they do not bind to decoy receptors that dampen apoptosis.

Advances in understanding apoptosis are opening new avenues for the development of pro-apoptotic therapies. By targeting the apoptosis pathway, Atrimer drug candidates may circumvent uncontrolled growth of malignant cells. For example, the pro-apoptotic receptor known as death receptor 4 (DR4) belongs to the trimeric TNF (tumor-necrosis-factor) superfamily of proteins widely expressed by cancer cells. The ligand that binds to DR4 and initiates cell death is known as TRAIL (TNF-related apoptosis-inducing ligand).

Atrimer drug candidates are designed to potently activate the DR4 receptor have been shown in preclinical studies to engage the DR4 pathway and cause cell death in a range of tumor types. Anaphore is focusing as well on activators of the related DR5 receptor and other potential pro-apoptotic therapies.

Atrimer™ conjugates: Delivering cancer-drug payloads

Image: Atrimer-drug conjugates hold the potential of better delivering anti-cancer agents to and within tumor cells.

Atrimer-drug conjugates hold the potential of better delivering anti-cancer agents to and within tumor cells.

The promise of the Atrimer technology in more effectively delivering other cancer drugs to and within tumor cells originates from another structural advantage of the Atrimer class. Atrimer drug candidates can be optimally constructed to retain in their terminal region a natural chain of amino acids in trimeric form perfectly suited for conjugation chemistry. Crucially, the chemical tethering of other drugs to this region does not disrupt the structure or binding properties of the molecule.

These conjugations can accommodate cytotoxic drugs and agents that overcome cellular mechanisms involved in either cancer causation or resistance to apoptosis. Early preclinical studies of Atrimer-drug conjugates have demonstrated their potential for superior efficacy against a variety of tumor types.

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