Marek Kovář
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View article: Stimuli-Sensitive Platinum-Based Anticancer Polymer Therapeutics: Synthesis and Evaluation In Vitro
Stimuli-Sensitive Platinum-Based Anticancer Polymer Therapeutics: Synthesis and Evaluation In Vitro Open
Background/Objectives: Here, we report the design, synthesis, and in vitro biological evaluation of a novel stimuli-sensitive nanotherapeutics based on cisplatin analog, cis-[PtCl2(NH3)(2-(3-oxobutyl)pyridine)] (Pt-OBP), covalently linked …
View article: Temporal optimization of CD25-biased IL-2 agonists and immune checkpoint blockade leads to synergistic anticancer activity despite robust regulatory T cell expansion
Temporal optimization of CD25-biased IL-2 agonists and immune checkpoint blockade leads to synergistic anticancer activity despite robust regulatory T cell expansion Open
Background Interleukin-2 (IL-2) immunotherapy can induce durable tumor remissions, but its clinical performance has been limited by significant drawbacks such as short serum half-life and high toxicity. Administration of IL-2 in complex wi…
View article: Novel PD-1-targeted, activity-optimized IL-15 mutein SOT201 acting in cis provides antitumor activity superior to PD1-IL2v
Novel PD-1-targeted, activity-optimized IL-15 mutein SOT201 acting in cis provides antitumor activity superior to PD1-IL2v Open
Background SOT201 and its murine surrogate mSOT201 are novel cis-acting immunocytokines consisting of a humanized/murinized/, Fc-silenced anti-programmed cell death protein 1 (PD-1) monoclonal antibody (mAb) fused to an attenuated human in…
View article: Overcoming P-glycoprotein-mediated multidrug resistance in cancer cells through micelle-forming PHPMA-b-PPO diblock copolymers for doxorubicin delivery
Overcoming P-glycoprotein-mediated multidrug resistance in cancer cells through micelle-forming PHPMA-b-PPO diblock copolymers for doxorubicin delivery Open
Multidrug resistance (MDR) represents one of the major concerns in cancer therapy as it may cause reduced efficacy of chemotherapeutic drugs due to the overexpression of ABC transporters, particularly P-glycoprotein (P-gp). This study expl…
View article: Figure 4 from Chemotherapy Drives Tertiary Lymphoid Structures That Correlate with ICI-Responsive TCF1<sup>+</sup>CD8<sup>+</sup> T Cells in Metastatic Ovarian Cancer
Figure 4 from Chemotherapy Drives Tertiary Lymphoid Structures That Correlate with ICI-Responsive TCF1<sup>+</sup>CD8<sup>+</sup> T Cells in Metastatic Ovarian Cancer Open
NACT positively increases the ICI-sensitive TCF1+PD1+CD8+ T-cell phenotype within metastatic HGSOC. A, Representative image of immunofluorescence of CD68, CD8, PD-L1, FoxP3, TCF1, CD57, PanCK, PD1, CD4, CD20, GZMB, and TIM-3 staining (immu…
View article: Figure 6 from Chemotherapy Drives Tertiary Lymphoid Structures That Correlate with ICI-Responsive TCF1<sup>+</sup>CD8<sup>+</sup> T Cells in Metastatic Ovarian Cancer
Figure 6 from Chemotherapy Drives Tertiary Lymphoid Structures That Correlate with ICI-Responsive TCF1<sup>+</sup>CD8<sup>+</sup> T Cells in Metastatic Ovarian Cancer Open
The clinical relevance of combined chemotherapy and immunotherapy in mouse models of TMBLo and TMBHi ovarian cancer. A and B, Bar plots showing single-nucleotide variants positions (SNVs) (A) and the somatic mutations prevalence (mutations…
View article: Figure 5 from Chemotherapy Drives Tertiary Lymphoid Structures That Correlate with ICI-Responsive TCF1<sup>+</sup>CD8<sup>+</sup> T Cells in Metastatic Ovarian Cancer
Figure 5 from Chemotherapy Drives Tertiary Lymphoid Structures That Correlate with ICI-Responsive TCF1<sup>+</sup>CD8<sup>+</sup> T Cells in Metastatic Ovarian Cancer Open
NACT-mediated progenitor TCF1+PD1+CD8+ T-cell phenotype associates with effector cytotoxic functions within metastatic HGSOC. A–C, Representative dot plot (A) and box plot (B) showing percentage of TIM-3+PD1+CD8+ T cells and GZMB+CD8+ T ce…
View article: Figure 1 from Chemotherapy Drives Tertiary Lymphoid Structures That Correlate with ICI-Responsive TCF1<sup>+</sup>CD8<sup>+</sup> T Cells in Metastatic Ovarian Cancer
Figure 1 from Chemotherapy Drives Tertiary Lymphoid Structures That Correlate with ICI-Responsive TCF1<sup>+</sup>CD8<sup>+</sup> T Cells in Metastatic Ovarian Cancer Open
Immunomodulation by NACT in metastatic HGSOC. A, Representative images of CALR immunostaining in CALRLo and CALRHi patients. Scale bars, 10 and 100 µm. B, CALR expression levels determined by immunostaining and (C) ER stress signature leve…
View article: Data from Chemotherapy Drives Tertiary Lymphoid Structures That Correlate with ICI-Responsive TCF1<sup>+</sup>CD8<sup>+</sup> T Cells in Metastatic Ovarian Cancer
Data from Chemotherapy Drives Tertiary Lymphoid Structures That Correlate with ICI-Responsive TCF1<sup>+</sup>CD8<sup>+</sup> T Cells in Metastatic Ovarian Cancer Open
Purpose:Patients with high-grade serous ovarian carcinoma (HGSOC) are virtually insensitive to immune checkpoint inhibitors (ICI) employed as standalone therapeutics, at least in part reflecting microenvironmental immunosuppression. Thus, …
View article: Figure 2 from Chemotherapy Drives Tertiary Lymphoid Structures That Correlate with ICI-Responsive TCF1<sup>+</sup>CD8<sup>+</sup> T Cells in Metastatic Ovarian Cancer
Figure 2 from Chemotherapy Drives Tertiary Lymphoid Structures That Correlate with ICI-Responsive TCF1<sup>+</sup>CD8<sup>+</sup> T Cells in Metastatic Ovarian Cancer Open
NACT-mediated adjuvanticity positively impacts clinically relevant TLS maturation in metastatic HGSOC. A, Representative image of immunofluorescence of CD4, CD8, CD20, CD21, CD23, DC-LAMP, and GZMB staining (immunofluorescence panel 1). Sc…
View article: Table 1 from Chemotherapy Drives Tertiary Lymphoid Structures That Correlate with ICI-Responsive TCF1<sup>+</sup>CD8<sup>+</sup> T Cells in Metastatic Ovarian Cancer
Table 1 from Chemotherapy Drives Tertiary Lymphoid Structures That Correlate with ICI-Responsive TCF1<sup>+</sup>CD8<sup>+</sup> T Cells in Metastatic Ovarian Cancer Open
Univariate Cox proportional hazard analyses.
View article: Figure 3 from Chemotherapy Drives Tertiary Lymphoid Structures That Correlate with ICI-Responsive TCF1<sup>+</sup>CD8<sup>+</sup> T Cells in Metastatic Ovarian Cancer
Figure 3 from Chemotherapy Drives Tertiary Lymphoid Structures That Correlate with ICI-Responsive TCF1<sup>+</sup>CD8<sup>+</sup> T Cells in Metastatic Ovarian Cancer Open
NACT-mediated adjuvanticity positively impacts the density of follicular T cells (TFH) and in situ activation of intratumoral B cells in mHGSOC. A–C, Representative image (A) and box plots showing the density of CD4+ cells (B) and CXCR5+PD…
View article: Supplementary Data1 from Chemotherapy Drives Tertiary Lymphoid Structures That Correlate with ICI-Responsive TCF1<sup>+</sup>CD8<sup>+</sup> T Cells in Metastatic Ovarian Cancer
Supplementary Data1 from Chemotherapy Drives Tertiary Lymphoid Structures That Correlate with ICI-Responsive TCF1<sup>+</sup>CD8<sup>+</sup> T Cells in Metastatic Ovarian Cancer Open
Supplemental material, figures and tables
View article: Dual Thermo- and pH-Responsive Polymer Nanoparticle Assemblies for Potential Stimuli-Controlled Drug Delivery
Dual Thermo- and pH-Responsive Polymer Nanoparticle Assemblies for Potential Stimuli-Controlled Drug Delivery Open
The development of stimuli-responsive drug delivery systems enables targeted delivery and environment-controlled drug release, thereby minimizing off-target effects and systemic toxicity. We prepared and studied tailor-made dual-responsive…
View article: Chemotherapy Drives Tertiary Lymphoid Structures That Correlate with ICI-Responsive TCF1+CD8+ T Cells in Metastatic Ovarian Cancer
Chemotherapy Drives Tertiary Lymphoid Structures That Correlate with ICI-Responsive TCF1+CD8+ T Cells in Metastatic Ovarian Cancer Open
Purpose: Patients with high-grade serous ovarian carcinoma (HGSOC) are virtually insensitive to immune checkpoint inhibitors (ICI) employed as standalone therapeutics, at least in part reflecting microenvironmental immunosuppression. Thus,…
View article: Engineered cytokine/antibody fusion proteins improve IL-2 delivery to pro-inflammatory cells and promote antitumor activity
Engineered cytokine/antibody fusion proteins improve IL-2 delivery to pro-inflammatory cells and promote antitumor activity Open
Progress in cytokine engineering is driving therapeutic translation by overcoming these proteins' limitations as drugs. The IL-2 cytokine is a promising immune stimulant for cancer treatment but is limited by its concurrent activation of b…
View article: Tertiary lymphoid structures and B cells determine clinically relevant T cell phenotypes in ovarian cancer
Tertiary lymphoid structures and B cells determine clinically relevant T cell phenotypes in ovarian cancer Open
Intratumoral tertiary lymphoid structures (TLSs) have been associated with improved outcome in various cohorts of patients with cancer, reflecting their contribution to the development of tumor-targeting immunity. Here, we demonstrate that…
View article: Chemosensitization of tumors via simultaneous delivery of STAT3 inhibitor and doxorubicin through HPMA copolymer-based nanotherapeutics with pH-sensitive activation
Chemosensitization of tumors via simultaneous delivery of STAT3 inhibitor and doxorubicin through HPMA copolymer-based nanotherapeutics with pH-sensitive activation Open
We synthesized three novel STAT3 inhibitors (S3iD1-S3iD3) possessing oxoheptanoic residue enabling linkage to HPMA copolymer carrier via a pH-sensitive hydrazone bond. HPMA copolymer conjugates bearing doxorubicin (Dox) and our STAT3 inhib…
View article: 1087 SOT201 is a novel cis-acting immunocytokine targeting IL-15Rβγ to reinvigorate PD-1<sup>+</sup>tumor infiltrating lymphocytes and potentiate anti-tumor efficacy
1087 SOT201 is a novel cis-acting immunocytokine targeting IL-15Rβγ to reinvigorate PD-1<sup>+</sup>tumor infiltrating lymphocytes and potentiate anti-tumor efficacy Open
Background SOT201 is a novel cis-acting immunocytokine consisting of a humanized, Fc-silenced monoclonal antibody against PD-1 fused to a covalent RLI-15 complex of a human attenuated IL-15 mutein linked to the high-affinity binding site o…
View article: Cultivar-dependent and drought-induced modulation of secondary metabolites, adaptative defense in Fagopyrum esculentum L
Cultivar-dependent and drought-induced modulation of secondary metabolites, adaptative defense in Fagopyrum esculentum L Open
The present study investigates the biochemical responses of buckwheat to drought stress, particularly focusing on phenolic acids and flavonoids, abundant in this crop. We hypothesize that distinct genotypic responses to drought stress will…
View article: Engineered cytokine/antibody fusion proteins improve delivery of IL-2 to pro-inflammatory cells and promote antitumor activity
Engineered cytokine/antibody fusion proteins improve delivery of IL-2 to pro-inflammatory cells and promote antitumor activity Open
Progress in cytokine engineering is driving therapeutic translation by overcoming the inherent limitations of these proteins as drugs. The interleukin-2 (IL-2) cytokine harbors great promise as an immune stimulant for cancer treatment. How…
View article: Regulatory T cells suppress the formation of potent KLRK1 and IL-7R expressing effector CD8 T cells by limiting IL-2
Regulatory T cells suppress the formation of potent KLRK1 and IL-7R expressing effector CD8 T cells by limiting IL-2 Open
Regulatory T cells (Tregs) are indispensable for maintaining self-tolerance by suppressing conventional T cells. On the other hand, Tregs promote tumor growth by inhibiting anti-cancer immunity. In this study, we identified that Tregs incr…
View article: Evaluation of linear versus star-like polymer anti-cancer nanomedicines in mouse models
Evaluation of linear versus star-like polymer anti-cancer nanomedicines in mouse models Open
Nanomedicines are considered next generation therapeutics with advanced therapeutic properties and reduced side effects. Herein, we introduce tailored linear and star-like water-soluble nanosystems as stimuli-sensitive nanomedicines for th…
View article: Author response: Regulatory T cells suppress the formation of potent KLRK1 and IL-7R expressing effector CD8 T cells by limiting IL-2
Author response: Regulatory T cells suppress the formation of potent KLRK1 and IL-7R expressing effector CD8 T cells by limiting IL-2 Open
Article Figures and data Abstract Editor's evaluation eLife digest Introduction Results Discussion Materials and methods Data availability References Decision letter Author response Article and author information Metrics Abstract Regulator…
View article: SOT101 induces NK cell cytotoxicity and potentiates antibody-dependent cell cytotoxicity and anti-tumor activity
SOT101 induces NK cell cytotoxicity and potentiates antibody-dependent cell cytotoxicity and anti-tumor activity Open
SOT101 is a superagonist fusion protein of interleukin (IL)-15 and the IL-15 receptor α (IL-15Rα) sushi+ domain, representing a promising clinical candidate for the treatment of cancer. SOT101 among other immune cells specifically stimulat…