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Combination Checkpoint Antibody Treatment in Cutaneous Squamous Cell Carcinoma

By: Kayci Reyer
Posted: Friday, August 27, 2021

According to research presented in Cancers, patients with cutaneous squamous cell carcinoma or its common precursor, actinic keratosis, who undergo a combination treatment of multiple checkpoint antibodies may experience improved outcomes. Though these patients often undergo surgical excision, Graham R. Leggatt, PhD, of the University of Queensland in Australia, and colleagues sought to determine whether checkpoints such as PD-1, V-domain Ig suppressor of T-cell activation (VISTA), and 4-1BB might be effective targets for immunotherapy in patients with multiple simultaneous lesions.

“Not all [actinic keratosis] or primary [cutaneous squamous cell carcinoma] are readily removed by surgery, and tumor recurrence can be problematic, suggesting that alternatives are needed as primary or supportive therapies. The high costs and systemic toxicities of these treatments may be circumvented by approaches that localize the antibodies to the tumor,” noted the authors.

In a previous phase II trial, many patients with cutaneous squamous cell carcinoma who were treated with the anti–PD-1 therapy cemiplimab-rwlc experienced a response. A total of 44% of patients with locally advanced disease and 47% of patients with metastatic disease achieved an objective response. Although this suggests that anti–PD-1 therapy may lead to improved clinical benefits, the treatment may be even more effective when paired with a co-inhibitory molecule, such as VISTA, or a costimulatory protein, like 4-1BB.

In previous studies, VISTA has been found to be expressed in cutaneous squamous cell skin cancer tissue. A combination treatment of anti–PD-1 and anti-VISTA antibodies may use multiple signaling pathways to attack tumors through an immune response. Another promising treatment option is anti–4-1BB therapy, which may be delivered as a monotherapy or in combination with anti–PD-1 treatment. Though data on this anti–4-1BB treatment in cutaneous skin cell carcinoma alone are limited, the treatment has been observed to activate antitumor T cells in many cancer types.

Disclosure: The study authors reported no conflicts of interest.



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