was doing bit more research comparing HER-Vaxx to Transtuzumab, interestingly Transtuzumab was approved in phase 3, will do more research on phase 2 for Transtuzumab and see how it compares with HER-Vaxx..HER-Vaxx
- Type: B-cell peptide-based vaccine.
- Mechanism of Action: HER-Vaxx is designed to stimulate the body's immune system to produce antibodies that target the HER2/neu receptor. It is a vaccine composed of short peptides derived from the extracellular domain of the HER2 protein, which can elicit a B-cell (antibody) immune response.
- Administration: HER-Vaxx is administered through injection, often in combination with standard chemotherapy.
- Early Study Results:
- Phase I: Demonstrated safety and the ability to elicit an immune response, with patients developing HER2-specific antibodies.
- Phase II: Early studies have shown that HER-Vaxx, combined with chemotherapy, can lead to improved clinical outcomes in terms of tumor shrinkage and progression-free survival in HER2-positive cancers.
- Key Benefits:
- The potential for a long-lasting immune response due to the generation of memory B-cells.
- May reduce the risk of tumor resistance seen with monoclonal antibody therapies like Trastuzumab.
- Limitations:
- As a novel vaccine, longer-term efficacy and safety data are still needed.
- Early studies are generally in small patient populations, requiring further validation in larger, randomized trials.
Trastuzumab (Herceptin)
- Type: Monoclonal antibody.
- Mechanism of Action: Trastuzumab is an engineered monoclonal antibody that specifically binds to the extracellular domain of the HER2 receptor, blocking downstream signaling pathways that promote tumor growth and survival. It also mediates antibody-dependent cellular cytotoxicity (ADCC).
- Administration: Intravenous infusion or subcutaneous injection, often combined with chemotherapy or other targeted agents.
- Early Study Results:
- Phase I and II: Demonstrated significant efficacy in HER2-positive breast cancer, with high response rates and improvements in progression-free and overall survival.
- Phase III: Pivotal studies (such as the CLEOPATRA trial) established Trastuzumab as a standard of care in HER2-positive breast cancer, showing a significant survival benefit.
- Key Benefits:
- Well-established with extensive clinical data supporting its use in various stages of HER2-positive breast cancer.
- Trastuzumab is approved for both early and metastatic HER2-positive breast cancer.
- Limitations:
- Development of resistance in some patients over time.
- Cardiotoxicity is a significant adverse effect, necessitating monitoring of cardiac function during treatment
I have compared them side by side based on their tech, B-cell Peptide-Based Vaccine which is HER-Vaxx if its sucessfull will be a game changer, I have highlighted which feature pips over the other, looks like B-cell Peptide-Based Vaccine will be successors of Monoclonal antibodies
Source Stimulates body's immune system to produce antibodies Lab-engineered antibodies administered directly
Mechanism Induces immune response to produce a polyclonal antibody mixture Directly binds to specific antigens with high specificity
Action Onset Slower onset (requires time for immune response) Immediate onset of action
Duration of Effect Potentially long-lasting due to immune memory Shorter duration, requires repeated dosing
Side Effects Generally fewer side effects Potential for more systemic side effects
Resistance Lower risk of resistance due to polyclonal response Higher risk of resistance due to single-target mechanism
Usage Control Less control over response variability among individuals Controlled dosing and administration
I see there are numerous monoclonal studies in play to improve on the shortcomings as aboveCancer Therapies
- T-DXd (Trastuzumab Deruxtecan): A conjugate of Trastuzumab linked to a cytotoxic chemotherapy agent (deruxtecan) currently being studied in various cancers, including HER2-positive breast cancer, gastric cancer, and other solid tumors. Trials are exploring its efficacy in patients with low HER2 expression as well.
- Pembrolizumab (Keytruda) and Nivolumab (Opdivo): Anti-PD-1 monoclonal antibodies are in numerous trials for a wide range of cancers, including melanoma, lung cancer, renal cell carcinoma, and head and neck cancers. These studies often combine PD-1 inhibitors with other treatments to explore synergies.
- Atezolizumab (Tecentriq) and Durvalumab (Imfinzi): Anti-PD-L1 monoclonal antibodies being studied in various cancers, often in combination with chemotherapy, other immunotherapies, or targeted therapies.
- Daratumumab (Darzalex): Targeting CD38, this monoclonal antibody is being studied in multiple myeloma in various combinations with other therapies to improve response rates and survival.
- Bispecific Antibodies (e.g., Blinatumomab): Blinatumomab targets CD19 and CD3, bridging T-cells to B-cell leukemias and lymphomas. Trials are exploring its use in relapsed or refractory acute lymphoblastic leukemia (ALL) and other B-cell malignancies
Type Antibody-drug conjugate (ADC) B-cell peptide-based vaccine
Mechanism of Action Combines HER2-targeted monoclonal antibody with chemotherapy Stimulates immune system to produce HER2-specific antibodies
Mode of Delivery Intravenous infusion Injection
Onset of Action Rapid, upon administration Slower, requires time for immune response
Efficacy High, particularly in heavily pretreated patients and in low HER2 expression Promising, particularly in combination with chemotherapy
Duration of Effect Limited to the period of drug administration Potentially long-lasting due to immune memory
Side Effects Higher, including risk of ILD and chemotherapy-related toxicities Generally fewer systemic side effects
Resistance Potential for resistance, though lower due to dual mechanism Lower risk of resistance due to polyclonal antibody response
Clinical Data Availability Extensive, with multiple Phase III trials completed Limited, early-phase trials with ongoing studies
Type Immune checkpoint inhibitors B-cell peptide-based vaccine
Mechanism of Action Blocks PD-1 pathway to enhance T-cell response Stimulates B-cells to produce HER2-specific antibodies
Target PD-1 receptor on T-cells HER2 receptor on cancer cells
Mode of Delivery Intravenous infusion Injection
Indications Multiple cancers (e.g., melanoma, lung, renal, head and neck) HER2-positive cancers (e.g., breast, gastric)
Onset of Action Rapid, within weeks of administration Slower, requires time for immune response
Efficacy High in certain cancers, especially with PD-L1 expression or high TMB Promising, particularly in combination with chemotherapy
Duration of Effect Potential for durable responses due to immune memory Potential for long-lasting immunity through memory B-cells
Side Effects Immune-related adverse events (irAEs), including severe inflammatory responses Generally fewer systemic side effects
Resistance Some patients do not respond; resistance may develop Lower risk of resistance due to polyclonal response
Clinical Data Availability Extensive, with numerous Phase III trials and approvals Limited, with ongoing early-phase trials
Type Immune checkpoint inhibitors B-cell peptide-based vaccine
Mechanism of Action Blocks PD-L1 pathway to enhance T-cell response Stimulates B-cells to produce HER2-specific antibodies
Target PD-L1 on tumor and immune cells HER2 receptor on cancer cells
Mode of Delivery Intravenous infusion Injection
Indications Multiple cancers (e.g., NSCLC, SCLC, bladder, breast, liver) HER2-positive cancers (e.g., breast, gastric)
Onset of Action Rapid, within weeks of administration Slower, requires time for immune response
Efficacy High in PD-L1 expressing tumors and some combinations Promising, particularly in combination with chemotherapy
Duration of Effect Potential for durable responses due to immune memory Potential for long-lasting immunity through memory B-cells
Side Effects Immune-related adverse events (irAEs), including severe inflammatory responses Generally fewer systemic side effects
Resistance Some patients do not respond; resistance may develop Lower risk of resistance due to polyclonal response
Clinical Data Availability Extensive, with numerous Phase III trials and approvals Limited, with ongoing early-phase trials
Feature Daratumumab (Darzalex) HER-Vaxx Type Monoclonal antibody B-cell peptide-based vaccine Mechanism of Action Targets CD38 to induce direct cell killing and immune modulation Stimulates B-cells to produce HER2-specific antibodies Target CD38 on multiple myeloma cells and some immune cells HER2 receptor on cancer cells Mode of Delivery Intravenous infusion or subcutaneous injection Injection Indications Multiple myeloma HER2-positive cancers (e.g., breast, gastric) Onset of Action Rapid, upon administration Slower, requires time for immune response Efficacy High in multiple myeloma, especially in relapsed/refractory settings Promising, particularly in combination with chemotherapy Duration of Effect Limited to the period of drug administration Potential for long-lasting immunity through memory B-cells Side Effects Infusion-related reactions, immunosuppression, increased infection risk Generally fewer systemic side effects Resistance Potential for resistance development over time Lower risk of resistance due to polyclonal antibody response Clinical Data Availability Extensive, with multiple Phase III trials and approvals Limited, with ongoing early-phase trials
Type Bispecific T-cell engager antibody B-cell peptide-based vaccine
Mechanism of Action Engages T-cells and B-cells by targeting CD19 and CD3 simultaneously Stimulates B-cells to produce HER2-specific antibodies
Target CD19 on B-cell malignancies and CD3 on T-cells HER2 receptor on cancer cells
Mode of Delivery Continuous intravenous infusion Injection
Indications B-cell malignancies (e.g., B-ALL) HER2-positive cancers (e.g., breast, gastric)
Onset of Action Rapid, due to direct T-cell engagement Slower, requires time for immune response
Efficacy High in relapsed/refractory B-cell malignancies Promising, particularly in combination with chemotherapy
Duration of Effect Short, requires continuous infusion Potential for long-lasting immunity through memory B-cells
Side Effects Cytokine release syndrome, neurotoxicity Generally fewer systemic side effects
Resistance Potential for resistance if CD19 expression is lost Lower risk of resistance due to polyclonal antibody response
Clinical Data Availability Extensive, particularly in hematologic malignancies Limited, with ongoing early-phase trials
