{"id":3421,"date":"2024-07-08T06:30:53","date_gmt":"2024-07-08T10:30:53","guid":{"rendered":"https:\/\/happylungsproject.org\/?p=3421"},"modified":"2026-03-02T10:53:31","modified_gmt":"2026-03-02T15:53:31","slug":"immunotherapy-and-ret-lung-cancer","status":"publish","type":"post","link":"https:\/\/happylungsproject.org\/immunotherapy-and-ret-lung-cancer\/","title":{"rendered":"Immunotherapy and RET Lung Cancer"},"content":{"rendered":"[vc_row type=”in_container” full_screen_row_position=”middle” column_margin=”default” column_direction=”default” column_direction_tablet=”default” column_direction_phone=”default” scene_position=”center” text_color=”dark” text_align=”left” row_border_radius=”none” row_border_radius_applies=”bg” overflow=”visible” overlay_strength=”0.3″ gradient_direction=”left_to_right” shape_divider_position=”bottom” bg_image_animation=”none” shape_type=””][vc_column column_padding=”no-extra-padding” column_padding_tablet=”inherit” column_padding_phone=”inherit” column_padding_position=”all” column_element_direction_desktop=”default” column_element_spacing=”default” desktop_text_alignment=”default” tablet_text_alignment=”default” phone_text_alignment=”default” background_color_opacity=”1″ background_hover_color_opacity=”1″ column_backdrop_filter=”none” column_shadow=”none” column_border_radius=”none” column_link_target=”_self” column_position=”default” gradient_direction=”left_to_right” overlay_strength=”0.3″ width=”1\/1″ tablet_width_inherit=”default” animation_type=”default” bg_image_animation=”none” border_type=”simple” column_border_width=”none” column_border_style=”solid”][vc_row_inner column_margin=”default” column_direction=”default” column_direction_tablet=”default” column_direction_phone=”default” text_align=”left” row_position=”default” row_position_tablet=”inherit” row_position_phone=”inherit” overflow=”visible” pointer_events=”all”][vc_column_inner column_padding=”padding-3-percent” column_padding_tablet=”inherit” column_padding_phone=”inherit” column_padding_position=”all” column_element_direction_desktop=”default” column_element_spacing=”default” desktop_text_alignment=”default” tablet_text_alignment=”default” phone_text_alignment=”default” background_color=”#f68d28″ background_color_opacity=”1″ background_hover_color_opacity=”1″ column_backdrop_filter=”none” font_color=”#ffffff” column_shadow=”none” column_border_radius=”10px” column_link_target=”_self” overflow=”visible” gradient_direction=”left_to_right” overlay_strength=”0.3″ width=”1\/1″ tablet_width_inherit=”default” animation_type=”default” bg_image_animation=”none” border_type=”simple” column_border_width=”none” column_border_style=”solid” column_padding_type=”default” gradient_type=”default”][vc_column_text css=”” text_direction=”default”]\n

Immunotherapy is a type of treatment that uses the body’s own immune system to fight cancer. Cancer cells start from healthy normal cells that become abnormal, and sometimes the immune system does not recognize abnormal cells\u00a0as foreign, making it difficult to target them. Immunotherapy helps to stimulate the immune system to better recognize and attack cancer cells.<\/span><\/p>\n[\/vc_column_text][\/vc_column_inner][\/vc_row_inner][vc_row_inner column_margin=”default” column_direction=”default” column_direction_tablet=”default” column_direction_phone=”default” text_align=”left” row_position=”default” row_position_tablet=”inherit” row_position_phone=”inherit” overflow=”visible” pointer_events=”all”][vc_column_inner column_padding=”no-extra-padding” column_padding_tablet=”inherit” column_padding_phone=”inherit” column_padding_position=”all” column_element_direction_desktop=”default” column_element_spacing=”default” desktop_text_alignment=”default” tablet_text_alignment=”default” phone_text_alignment=”default” background_color_opacity=”1″ background_hover_color_opacity=”1″ column_backdrop_filter=”none” column_shadow=”none” column_border_radius=”none” column_link_target=”_self” overflow=”visible” gradient_direction=”left_to_right” overlay_strength=”0.3″ width=”1\/1″ tablet_width_inherit=”default” animation_type=”default” bg_image_animation=”none” border_type=”simple” column_border_width=”none” column_border_style=”solid”][vc_column_text css=”” text_direction=”default”]\n

The immune system defends the body against infections. It can identify and attack different pathogens that the body does not recognize as its own like bacteria, viruses, or fungi, and it is also able to identify and attack cancer cells.<\/p>\n

Immune Checkpoint Inhibitors: Taking Off the Immune System \u2018Brakes\u2019 for Cancer Treatment<\/h2>\n

There are several types of immunotherapies that have been developed to treat cancer<\/a> including the immune checkpoint inhibitors (or immune checkpoint blockade) such as anti-PD-1\/PD-L1 or anti-CTLA4. These were approved for the treatment of non-small cell lung cancer (NSCLC) alone or in combination with chemotherapy (ipilimumab, nivolumab, pembrolizumab, durvalumab, atezolizumab, and cemiplimab) (1). These drugs fight cancer by taking off the \u2018brakes\u2019 of immune cells, allowing them to effectively attack and destroy cancer cells.<\/p>\n

In 2018, the Nobel Prize in Physiology or Medicine was awarded to Drs. James Allison and Tasuku Honjo for their work on the CTLA-4 molecule and the development of the first-in-class antibody that could bind to CTLA-4 and block its function (Ipilimumab) (2).<\/p>\n

Checkpoint blockade inhibitors have shown great and durable responses in NSCLC patients, especially in patients who presented high levels of PD-L1 expression and\/or high number of mutations (called tumor mutation burden (TMB) in their tumors. These drugs have revolutionized the treatment of NSCLC, but they do not always work for every NSCLC patient. Researchers are studying the factors that determine which patients are more likely to respond to immune checkpoint blockade treatment and which patients are less likely to respond. Hopefully, with additional research, immunotherapy will become a more reliable way to treat cancer.<\/p>\n

Immune Checkpoint Blockade Immunotherapy for RET NSCLC<\/h2>\n

Several studies and clinical trials have established the efficacy of immune checkpoint blockade therapies in NSCLC patients. Despite this, studies have shown that immune system checkpoint inhibitors alone have low efficacy to fight cancer in the treatment of patients with NSCLC with oncogenic-driven tumors such as EGFR, ALK, ROS1, or RET (3-5).<\/p>\n

For RET NSCLC, one explanation of this low efficacy may be that RET lung cancers are characterized by having low levels of PD-L1 expression and low TMB in the majority of patients (3). Because of this, other therapeutic strategies such as RET targeted therapy should be considered before administering immunotherapy alone for the treatment of patients with RET alterations.<\/p>\n

Other Immunotherapies<\/h2>\n

Besides immune checkpoint blockade immunotherapy, there are other types of immunotherapy treatments that use different strategies to enhance immune system response to better recognize and kill cancer cells.[\/vc_column_text][\/vc_column_inner][\/vc_row_inner][toggles style=”minimal_shadow” accordion=”true” accordion_starting_functionality=”closed” border_radius=”none”][toggle color=”Accent-Color” heading_tag=”h3″ heading_tag_functionality=”default” title=”1. Adoptive Cellular Therapies (ACT)”][vc_column_text css=”” text_direction=”default”]ACT is another class of cancer immunotherapy based on the isolation of the immune T cells that can recognize tumors, their expansion in the lab, and the re-infusion of the selected immune T cells back into cancer patients. There are several different types of ACTs:<\/p>\n

Chimeric antigen receptor (CAR) T-cell therapy<\/strong><\/h4>\n

In CAR T-cell therapy, the immune T-cells are taken from a patient\u2019s blood and re-engineered in the lab to express a receptor called Chimeric Antigen Receptor (CAR) that specifically binds to a surface protein that is present in the cancer cells. These CAR T-cells are expanded in the laboratory and infused back to the patient. CAR T-cell therapy has been successful in treating some blood cancers like leukemias or lymphomas, and it is being studied in clinical trials for the treatment of solid tumors.<\/p>\n

Tumor-infiltrating lymphocytes (TIL) therapy<\/strong><\/h4>\n

TIL therapy uses the T cells that are found in patient\u2019s tumors, which are called\u00a0tumor-infiltrating lymphocytes\u00a0or TILs. These TILs are analyzed to identify the ones which recognize and attack the tumor cells. When the best TILs are selected, they are expanded and infused back to patients. TIL therapies rely on patient\u2019s tumor biopsies as the biopsies as the TILs are isolated from the tumor biopsies. TIL therapy has proven efficacious in patients with melanoma and other solid tumors (6) and is under investigation for the treatment of NSCLC patients (7).<\/p>\n

T-cell receptor (TCR) therapy<\/strong><\/h4>\n

In contrast to CAR T-cell therapy, which uses T cells that recognize a specific protein expressed on the surface of a tumor cell, TCR T-cell therapy utilizes T cells that can recognize any protein expressed on tumors (intracellular or surface proteins). TCR T-cell therapy utilizes the immune T cells from a patient\u2019s blood that are re-engineered in the lab to express a specific TCR that binds to proteins expressed in the cancer cells. This therapy has been proven effective in some cancers expressing including KRAS mutant cancers (8).<\/p>\n