[vc_row type=”full_width_background” full_screen_row_position=”middle” bg_color=”#ffffff” scene_position=”center” text_color=”dark” text_align=”left” top_padding=”3%” bottom_padding=”3%” overlay_strength=”0.5″ shape_divider_position=”bottom” bg_image_animation=”none” shape_type=””][vc_column column_padding=”no-extra-padding” column_padding_position=”all” background_color_opacity=”1″ background_hover_color_opacity=”1″ column_link_target=”_self” column_shadow=”none” column_border_radius=”none” width=”1/1″ tablet_width_inherit=”default” tablet_text_alignment=”default” phone_text_alignment=”default” column_border_width=”none” column_border_style=”solid” bg_image_animation=”none”][vc_row_inner column_margin=”default” text_align=”left”][vc_column_inner column_padding=”no-extra-padding” column_padding_position=”all” background_color_opacity=”1″ background_hover_color_opacity=”1″ column_shadow=”none” column_border_radius=”none” column_link_target=”_self” width=”1/1″ tablet_width_inherit=”default” column_border_width=”none” column_border_style=”solid” bg_image_animation=”none”][vc_custom_heading text=”Recent progress” font_container=”tag:h2|text_align:left|line_height:50px” use_theme_fonts=”yes”][/vc_column_inner][/vc_row_inner][vc_row_inner column_margin=”default” text_align=”left”][vc_column_inner column_padding=”no-extra-padding” column_padding_position=”all” background_color_opacity=”1″ background_hover_color_opacity=”1″ column_shadow=”none” column_border_radius=”none” column_link_target=”_self” width=”1/2″ tablet_width_inherit=”default” column_border_width=”none” column_border_style=”solid” bg_image_animation=”none”][image_with_animation image_url=”8038″ alignment=”” animation=”None” img_link_target=”_blank” border_radius=”none” box_shadow=”none” max_width=”100%” img_link=”https://hamletbiopharma.com/wp-content/uploads/2021/12/Mol-Cell-Oncol-2021.pdf”][/vc_column_inner][vc_column_inner column_padding=”no-extra-padding” column_padding_position=”all” background_color_opacity=”1″ background_hover_color_opacity=”1″ column_shadow=”none” column_border_radius=”none” column_link_target=”_self” width=”1/2″ tablet_width_inherit=”default” column_border_width=”none” column_border_style=”solid” bg_image_animation=”none”][vc_column_text]
The protein-lipid complex alpha1-oleate, derived from HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells), is identified as a molecular entity with significant therapeutic potential. Structural characterization of the complex and results of a successful placebo-controlled clinical trial are presented.
[/vc_column_text][/vc_column_inner][/vc_row_inner][/vc_column][/vc_row][vc_row type=”in_container” full_screen_row_position=”middle” scene_position=”center” text_color=”dark” text_align=”left” overlay_strength=”0.3″ shape_divider_position=”bottom” bg_image_animation=”none”][vc_column column_padding=”no-extra-padding” column_padding_position=”all” background_color_opacity=”1″ background_hover_color_opacity=”1″ column_link_target=”_self” column_shadow=”none” column_border_radius=”none” width=”1/3″ tablet_width_inherit=”default” tablet_text_alignment=”default” phone_text_alignment=”default” column_border_width=”none” column_border_style=”solid” bg_image_animation=”none”][image_with_animation image_url=”7845″ alignment=”” animation=”None” border_radius=”none” box_shadow=”none” max_width=”100%” img_link=”https://www.nature.com/articles/s41467-021-23748-y”][vc_column_text]
[/vc_column_text][vc_column_text]
Partially unfolded alpha-lactalbumin forms the oleic acid complex HAMLET, with potent tumoricidal activity. Here we define a peptide-based molecular approach for targeting and killing tumor cells, and evidence of its clinical potential (ClinicalTrials.gov NCT03560479). A 39-residue alpha-helical peptide from alpha-lactalbumin is shown to gain lethality for tumor cells by forming oleic acid complexes (alpha1-oleate). Nuclear magnetic resonance measurements and computational simulations reveal a lipid core surrounded by conformationally fluid, alpha-helical peptide motifs. In a single center, placebo controlled, double blinded Phase I/II interventional clinical trial of non-muscle invasive bladder cancer, all primary end points of safety and efficacy of alpha1-oleate treatment are reached, as evaluated in an interim analysis. Intra-vesical instillations of alpha1-oleate triggers massive shedding of tumor cells and the tumor size is reduced but no drug-related side effects are detected (primary endpoints). Shed cells contain alpha1-oleate, treated tumors show evidence of apoptosis and the expression of cancer-related genes is inhibited (secondary endpoints). The results are especially encouraging for bladder cancer, where therapeutic failures and high recurrence rates create a great, unmet medical need.[/vc_column_text][/vc_column][vc_column column_padding=”no-extra-padding” column_padding_position=”all” background_color_opacity=”1″ background_hover_color_opacity=”1″ column_link_target=”_self” column_shadow=”none” column_border_radius=”none” width=”1/3″ tablet_width_inherit=”default” tablet_text_alignment=”default” phone_text_alignment=”default” column_border_width=”none” column_border_style=”solid” bg_image_animation=”none”][image_with_animation image_url=”7911″ alignment=”” animation=”None” border_radius=”none” box_shadow=”none” max_width=”100%”][image_with_animation image_url=”7909″ alignment=”” animation=”None” border_radius=”none” box_shadow=”none” max_width=”100%” img_link=”https://onlinelibrary.wiley.com/doi/10.1002/ijc.33019″][vc_column_text]
[/vc_column_text][vc_column_text]
Potent chemotherapeutic agents are required to counteract the aggressive behavior of cancer cells and patients often experience severe side effects, due to tissue toxicity. Our study addresses if a better balance between efficacy and toxicity can be attained using the tumoricidal complex alpha1-oleate, formed by a synthetic, alpha-helical peptide comprising the N-terminal 39 amino acids of alpha-lactalbumin and the fatty acid oleic acid. Bladder cancer was established, by intravesical instillation of MB49 cells on day 0 and the treatment group received five instillations of alpha1-oleate (1.7-17 mM) on days 3 to 11. A dose-dependent reduction in tumor size, bladder size and bladder weight was recorded in the alpha1-oleate treated group, compared to sham-treated mice. Tumor markers Ki-67, Cyclin D1 and VEGF were inhibited in a dose-dependent manner, as was the expression of cancer-related genes. Remarkably, toxicity for healthy tissue was not detected in alpha1-oleate-treated, tumor-bearing mice or healthy mice or rabbits, challenged with increasing doses of the active complex. The results define a dose-dependent therapeutic effect of alpha1-oleate in a murine bladder cancer model.
[/vc_column_text][/vc_column][vc_column column_padding=”no-extra-padding” column_padding_position=”all” background_color_opacity=”1″ background_hover_color_opacity=”1″ column_link_target=”_self” column_shadow=”none” column_border_radius=”none” width=”1/3″ tablet_width_inherit=”default” tablet_text_alignment=”default” phone_text_alignment=”default” column_border_width=”none” column_border_style=”solid” bg_image_animation=”none”][image_with_animation image_url=”7913″ alignment=”right” animation=”None” border_radius=”none” box_shadow=”none” max_width=”100%”][image_with_animation image_url=”7914″ alignment=”” animation=”None” border_radius=”none” box_shadow=”none” max_width=”100%” img_link=”https://academic.oup.com/mbe/article/37/11/3083/5855678″][vc_column_text]
[/vc_column_text][vc_column_text]
A challenging question in evolutionary theory is the origin of cell division and plausible molecular mechanisms involved. Here, we made the surprising observation that complexes formed by short alpha-helical peptides and oleic acid can create multiple membrane-enclosed spaces from a single lipid vesicle. The findings suggest that such complexes may contain the molecular information necessary to initiate and sustain this process. Based on these observations, we propose a new molecular model to understand protocell division.
[/vc_column_text][/vc_column][/vc_row][vc_row type=”in_container” full_screen_row_position=”middle” scene_position=”center” text_color=”dark” text_align=”left” overlay_strength=”0.3″ shape_divider_position=”bottom” bg_image_animation=”none”][vc_column column_padding=”no-extra-padding” column_padding_position=”all” background_color_opacity=”1″ background_hover_color_opacity=”1″ column_link_target=”_self” column_shadow=”none” column_border_radius=”none” width=”1/1″ tablet_width_inherit=”default” tablet_text_alignment=”default” phone_text_alignment=”default” column_border_width=”none” column_border_style=”solid” bg_image_animation=”none”][image_with_animation image_url=”7833″ alignment=”” animation=”None” border_radius=”none” box_shadow=”none” max_width=”100%” margin_top=”30″][vc_column_text]
Graphic illustration of the mode of action of HAMLET/Alpha1H in the cell (describing the steps towards tumour cell death). Source: Hamlet Pharma.
[/vc_column_text][/vc_column][/vc_row][vc_row type=”in_container” full_screen_row_position=”middle” scene_position=”center” text_color=”dark” text_align=”left” overlay_strength=”0.3″ shape_divider_position=”bottom” bg_image_animation=”none”][vc_column column_padding=”no-extra-padding” column_padding_position=”all” background_color_opacity=”1″ background_hover_color_opacity=”1″ column_link_target=”_self” column_shadow=”none” column_border_radius=”none” width=”1/1″ tablet_width_inherit=”default” tablet_text_alignment=”default” phone_text_alignment=”default” column_border_width=”none” column_border_style=”solid” bg_image_animation=”none”][divider line_type=”Small Line” line_alignment=”center” line_thickness=”1″ divider_color=”default” custom_height=”30″][/vc_column][/vc_row]