ABSTRACT
Coronavirus Papain-like protease (PLpro) mediates the cleavage of viral polyproteins and assists the virus escaping from innate immune response. Thus, PLpro is an attractive target for the development of broad-spectrum drugs as it has a conserved structure across different coronaviruses. In this study, we purified SARS-CoV-2 PLpro as an immune antigen, constructed a nanobody phage display library, and identified a set of nanobodies with high affinity for SARS-CoV-2. In addition, enzyme activity experiments demonstrated that two nanobodies had a significant inhibitory effect on the PLpro. These nanobodies should therefore be investigated as candidates for the treatment of coronaviruses.
Subject(s)
COVID-19 , Single-Domain Antibodies , Humans , Coronavirus Papain-Like Proteases , SARS-CoV-2 , Peptide Hydrolases , Papain/chemistryABSTRACT
Immunotherapy has been a new standard for recurrent/metastatic head and neck cancers (R/M HNC). One of the prominent characteristics of cancer immunotherapy is the induction of immune memory followed by endured treatment response. However, whether and how a treatment delay would impact on the efficacy of immunotherapy has not been well determined. During the outbreak of COVID-19, a number of cancer patients in Wuhan, the epicenter of the pandemic in China, had experienced long-lasting city lockdown and delay of immunotherapies. Here, we retrospectively analyzed 24 HNC patients treated with immune checkpoint inhibitors in our cancer institute prior to the outbreak of COVID-19 who were re-evaluated after the restoration of regular medical care. Of these 24 patients, 10 patients had achieved complete response (CR) or partial response (PR), 12 patients had achieved stable disease (SD), and 2 patients had received just one cycle treatment without efficacy evaluation before treatment delay. The median delay was 3.75 months (range 1.73-8.17 months). Re-evaluation after treatment delay revealed that ten patients (10/10) who achieved CR or PR, two patients (2/2) who received just one cycle treatment without efficacy evaluation and seven patients (7/12) who achieved SD before outbreak of COVID-19 maintained tumor response after treatment delay. Among the rest five patients who had achieved SD, four patients were re-evaluated as progressive disease (PD) due to treatment delay and one patient died after treatment interruption without re-evaluation. Our results from a small cohort of R/M HNC patients showed that treatment delay of three to four months might have mild, if any, impact on the efficacy of immunotherapy for patients with controlled disease.
Subject(s)
COVID-19/physiopathology , Carcinoma, Squamous Cell/therapy , Head and Neck Neoplasms/therapy , Immune Checkpoint Inhibitors/therapeutic use , Immunotherapy/methods , Adult , Aged , COVID-19/epidemiology , COVID-19/virology , Carcinoma, Squamous Cell/immunology , Carcinoma, Squamous Cell/pathology , China , Female , Head and Neck Neoplasms/immunology , Head and Neck Neoplasms/pathology , Humans , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Recurrence, Local , Pandemics , Retrospective Studies , SARS-CoV-2/physiology , Time-to-Treatment , Treatment OutcomeABSTRACT
Combined immune checkpoint inhibitor with platinum-based doublet chemotherapy brought about significant improvement in overall survival as the first line treatment in metastatic and recurrent head and neck cancer patients. However, in elderly patients with relatively poor performance status, these regimens might not be well tolerated. Therefore, we evaluated the safety and effect of combined immunotherapy and single agent chemotherapy in an elderly patient with recurrent head and neck squamous cell carcinoma. A 78-year-old male patients with a repeatedly recurrent gingival squamous cell carcinoma was admitted in our institute. Previously this patient underwent two consecutive surgical resections of recurrent tumors before the second rapid recurrence that resulted in extended tumor mass and lymph node metastasis. As the patient was in a relatively poor performance status (performance status =2), immunotherapy with PD-1 antibody (Toripalimab) combined with single agent chemotherapy (two cycle with albumin-bound paclitaxel and then six cycles with gemcitabine) was administrated, which led to clinical complete response after 8 cycles of treatment. The patient continued 4 cycles of maintenance immunotherapy with Toripalimab until the outbreak of the coronavirus disease 2019. The treatment was well tolerated and the patient remained free from disease until the last follow up by June 2020, 16 months after the initiation of treatment. The success in this case indicated that the combination of anti-PD-1 antibody and single chemotherapy agent may also be effective as well as safe in elderly patients with recurrent head and neck squamous cell carcinoma.