Antibody-drug conjugate (ADC) targeting antigens expressed on the surface of tumor cells are an effective approach for delivering drugs into the cells via antigen-mediated endocytosis. One of the well-known tumor antigens, the CD20 of B-lymphocyte, has long been suggested to be noninternalizing epitope, and is thus not considered a desirable target for ADCs. Here, sortase A (srtA)-mediated transpeptidation is used to specifically conjugate triple glycine-modified monomethyl auristatin E (MMAE), a highly toxic antimitotic agent, to anti-CD20 ofatumumab (OFA) equipped with a short C-terminal LPETG (5 amino acids) tag at heavy chain (HL), which generates ADCs that show extremely strong potency in killing CD20 positive cancer cells. One of the srtA-generated ADCs with a cleavable dipeptide linker (valine-citrulline, vc), OFA-HL-vcMMAE, shows IC50 values ranging from 5 pg mL to 4.1 ng mL against CD20+ lymphoma cells. Confocal laser scanning microscopy confirms that OFA-HL-vcMMAE internalization by Ramos cells is significantly improved compared to OFA alone, consistent with the high antitumor activity of the new ADC. OFA-HL-vcMMAE, at 5 mg kg dose, is able to eliminate tumors with mean volume ≈400 mm while no obvious drug-related toxicity is observed. The results show that srtA-generated OFA-MMAE conjugate system provides a viable strategy for targeting CD20+ B lineage lymphomas.

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Background: A satisfactory biopsy determines the state-of-the-art management of lung cancer in this era of personalized medicine. This study aimed to investigate the suitability and efficacy of computed tomography (CT)-guided core needle biopsy in clinical management. Methods: A cohort of 353 patients with clinically suspected lung cancer was enrolled in the study. Patient factors and biopsy variables were recorded. Epidermal growth factor receptor (EGFR) gene mutations and echinoderm microtubuleassociated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) rearrangement were detected in tumor specimens. Adequacy of biopsic obtainment for clinical trial screening and tissue bank establishment were reviewed. Results: Overall diagnostic accuracy of malignancy achieved 98.5%. The median biopsy time of the cohort was 20 minutes. In patients with non-small cell lung cancer (NSCLC), 99.3% (287/289) were diagnosed as specific histologic subtypes, and two patients (0.7%) were determined as NSCLC not otherwise specified (NOS). EGFR mutations were analyzed in 81.7% (236/289) of patients with NSCLC, and 98.7% (233/236) showed conclusive results. EML4-ALK gene fusion was tested in 43.9% (127/289) of NSCLC patients, and 98.4% (125/127) showed conclusive results: 6.4% (8/125) of those had gene fusion. Ninety-six NSCLC patients participated in clinical trial screening and provided mandatory tumor slides for molecular profiling. Pathological evaluation was fulfilled in 90 patients (93.8%); 99.4% (320/322) of patients with malignancy provided extra tissue for the establishment of a tumor bank. Conclusions: CT-guided core needle biopsy provided optimal clinical management in this era of translational medicine. The biopsic modality should be prioritized in selected lung cancer patients.

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