On-treatment blood TMB as predictors for camrelizumab plus chemotherapy in advanced lung squamous cell carcinoma: biomarker analysis of a phase III trial

Background: Camrelizumab plus chemotherapy significantly prolonged progression-free survival (PFS) and overall survival (OS) compared to chemotherapy alone as first-line treatment in advanced lung squamous cell carcinoma (LUSC) in the phase III trial (CameL-sq), which has become an option of standard-of-cares for Chinese patients with advanced LUSC. However, the predictive biomarkers remain unknown.
Methods: Tumor tissue samples at baseline, and peripheral blood samples at baseline (pretreatment) and after two cycles of treatment (on-treatment) were prospectively collected from 270 LUSC patients from the CameL-sq study. Blood tumor mutation burden (bTMB) and its dynamics were analyzed to explore their predictive values.
Results: Pretreatment bTMB was not associated with objective response, PFS and OS in camrelizumab or placebo plus chemotherapy groups. Low on-treatment bTMB was associated with significantly better objective response (73.8% vs 27.8%, P < 0.001), PFS (median, 9.1 vs 4.1 months; P < 0.001) and OS (median, not reached vs 8.0 months; P < 0.001) in camrelizumab plus chemotherapy group whereas it did not correlate with objective response and PFS in chemotherapy alone group. Importantly, on-treatment bTMB level could discriminate patients of initially radiological stable disease who would long-term benefit from camrelizumab plus chemotherapy (low vs high, median OS, 18.2 vs 7.8 months; P = 0.001). Combing on-treatment bTMB and its dynamics improved the ability for predicting the efficacy of camrelizumab plus chemotherapy.
Conclusion: On-treatment bTMB together with its dynamics could serve as a predictive biomarker for camrelizumab plus chemotherapy in patients with advanced LUSC.

High-efficiency application of CTS-Co NPs mimicking peroxidase enzyme on TMB(ox)

In this study, analytical studies of Chitosan-Cobalt(II) (CTS-Co(II)) nanoparticles (CTS – Co NPs) by mimicking horseradish peroxidase (HRP) were evaluated. In the applications, it was observed that CTS-Co NPs 3,3′ 5,5′ tetramethylbenzidine (TMB) oxidized in the presence of hydrogen peroxide (H2O2). The required CTS-Co NPs were synthesized at 50 °C in 30 min and characterized using Fourier transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), inductively coupled plasma-optical emission spectroscopy (ICP-OES), and X-ray photon spectroscopy (XPS) was done. CTS-Co NPs were studied to develop a selective TMB biosensor on TMB(ox) substrate. The synthesized CTS-Co NPs formed a catalytic reaction with 30% 0.2 mM H2O2 on 0.2 M TMB substrate. After the catalytic reaction, sensitive signals were obtained from the desired biosensor. Electrochemical measurements were taken as low limit of 10 mg and a high limit of 20 mg for the determination of CTS-Co NPs to TMB(ox). In the microplate study; The sensors were applied on 1.5 μg and 3 μg CTS-Co NPs TMB(ox) substrate, respectively. CTS- Co NPs; for TMB(ox) determination, optical density (OD) measurement was taken as a low limit of 1.5 μg and a high limit of 3 μg. Electrochemical applications of particles and microplate reader results were compared with horseradish peroxidase (HRP) enzyme for sensor properties. According to the data obtained, it was observed that it behaved similarly to the CTS-Co NPs peroxidase enzyme. This work presents innovations for nanoparticle extraction and sensor study from chitosan and other naturally sourced polymers.

Real-world application of tumor mutational burden-high (TMB-high) and microsatellite instability (MSI) confirms their utility as immunotherapy biomarkers

Introduction: Microsatellite instability (MSI) testing and tumor mutational burden (TMB) are genomic biomarkers used to identify patients who are likely to benefit from immune checkpoint inhibitors. Pembrolizumab was recently approved by the Food and Drug Administration for use in TMB-high (TMB-H) tumors, regardless of histology, based on KEYNOTE-158. The primary objective of this retrospective study was real-world applicability and use of immunotherapy in TMB/MSI-high patients to lend credence to and refine this biomarker.
Methods: Charts of patients with advanced solid tumors who had MSI/TMB status determined by next generation sequencing (NGS) (FoundationOne CDx) were reviewed. Demographics, diagnosis, treatment history, and overall response rate (ORR) were abstracted. Progression-free survival (PFS) was determined from Kaplan-Meier curves. PFS1 (chemotherapy PFS) and PFS2 (immunotherapy PFS) were determined for patients who received immunotherapy after progressing on chemotherapy. The median PFS2/PFS1 ratio was recorded.
Results: MSI-high or TMB-H [≥20 mutations per megabase (mut/MB)] was detected in 157 adults with a total of 27 distinct tumor histologies. Median turnaround time for NGS was 73 days. ORR for most recent chemotherapy was 34.4%. ORR for immunotherapy was 55.9%. Median PFS for patients who received chemotherapy versus immunotherapy was 6.75 months (95% confidence interval, 3.9-10.9 months) and 24.2 months (95% confidence interval, 9.6 months to not reached), respectively (P = 0.042). Median PFS2/PFS1 ratio was 4.7 in favor of immunotherapy.
Conclusion: This real-world study reinforces the use of TMB as a predictive biomarker. Barriers exist to the timely implementation of NGS-based biomarkers and more data are needed to raise awareness about the clinical utility of TMB. Clinicians should consider treating TMB-H patients with immunotherapy regardless of their histology.

TMB and TCR Are Correlated Indicators Predictive of the Efficacy of Neoadjuvant Chemotherapy in Breast Cancer

Immune characteristics were reported correlated to benefit neoadjuvant chemotherapy (NAC) in breast cancer, yet integration of comprehensive genomic alterations and T-cell receptors (TCR) to predict efficacy of NAC needs further investigation. This study simultaneously analyzed TMB (Tumor Mutation Burden), TCRs, and TILs (tumor infiltrating lymphocyte) in breast cancers receiving NAC was conducted in a prospective cohort (n = 22). The next-generation sequencing technology-based analysis of genomic alterations and TCR repertoire in paired breast cancer samples before and after NAC was conducted in a prospective cohort (n = 22). Fluorescent multiplex immunohistochemistry was used to stain CD4, CD8, PD1, TIM3, and cytokeratins simultaneously in those paired samples. TMB in pretreatment tumor tissues and TCR diversity index are higher in non-pCR patients than in pCR patients (10.6 vs. 2.3; p = 0.043) (2.066 vs. 0.467; p = 0.010). TMB and TCR diversity index had linear correlation (y = 5.587x – 0.881; r = 0.522, p = 0.012). Moreover, infiltrating T cells are significantly at higher presence in pCR versus non-pCR patients.
Dynamically, the TMB reduced significantly after therapy in non-pCR patients (p = 0.010) but without TCR index change. The CDR3 peptide AWRSAGNYNEQF is the most highly expressed in pre-NAC samples of pCR patients and in post-NAC samples of non-pCR patients. In addition to pCR, high clonality of TCR and high level of CD8+ expression are associated with disease-free survival (DFS). TCR index and TMB have significant interaction and may guide neo-adjuvant treatment in operable breast cancers. Response to NAC in tumors with high TCR clonality may be attributable to high infiltration and expansion of tumor-specific CD8 positive effector cells.

TMB,

30159789 Tecan Benelux 1 unit 60.53 EUR

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HY-15930 MedChemExpress 5g 241.2 EUR

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AR-8221-01 ImmunoBioscience 50 ml 47.75 EUR

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AR-8221-02 ImmunoBioscience 100 ml 79.65 EUR

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AR-8221-04 ImmunoBioscience 500 ml 222.6 EUR

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C6996-1000 ApexBio 1g 368 EUR

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C6996-500 ApexBio 500mg 224 EUR

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20-abx082290 Abbexa
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TMB 2Hcl

20-abx082418 Abbexa
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TMB-PS

T7109-10mg TargetMol Chemicals 10mg Ask for price

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TMB-PS

HY-15931 MedChemExpress 10mM/1mL 606 EUR

TMB 2Hcl

abx082290-100l Abbexa 100 µl 162.5 EUR

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abx082290-1ml Abbexa 1 ml Ask for price

TMB 2Hcl

abx082290-200l Abbexa 200 µl 212.5 EUR

TMB 2Hcl

abx082418-100l Abbexa 100 µl 125 EUR

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abx082418-1ml Abbexa 1 ml Ask for price

TMB 2Hcl

abx082418-200l Abbexa 200 µl 200 EUR

Colorimetry /SERS dual-sensor of H 2 O 2 constructed via TMB-Fe 3 O 4@ AuNPs

Hydrogen peroxide (H2O2) detection with high sensitivity plays an important role in biomedical research and food engineering. By combining colorimetry and surface enhanced Raman spectroscopy (SERS), we synthetize a novel H2O2 dual-sensor constructed via TMB-Fe3O4@AuNPs. In the presence of H2O2, the peroxide model enzyme might catalyze the oxidation of 3,3′,5,5′- tetramethylbenzidine (TMB) as blue charge transfer complex (CTC) for colorimetry, and then facilitate the sensitivity improvement of SERS detection. The achieved results show that in colorimetry, the linear range is from 40 μM to 5.5 mM with the detection limit of 11.1 μM; in SERS detection, the linear range is from 2 nM to 1 μM with the detection limit of 0.275 nM. Clearly, this mutual reference strategy improves both the detection limit of colorimetry and the sensitivity of SERS detection. Moreover, this colorimetry/SERS dual-sensor constructed via TMB-Fe3O4@AuNPs is successfully applied to the H2O2 detection in plasma and milk, indicating the excellent performance and flexibility.

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