Immunotherapy
Harnessing the power of plasmid DNA and viral vectors for life-saving treatments
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Patients suffering from diseases caused by harmful antigens and pathogens now have more treatment options than ever, thanks to advancements in plasmid DNA and viral vector based therapies.
What exactly are immunotherapies and how do plasmid DNA and viral vectors play a role? We are glad you asked!
Immunotherapy is a treatment approach that leverages the body’s immune system to fight diseases, increasingly cancer diseases. It works by either stimulating the immune system to attack cancer cells more effectively or by providing components, such as antibodies, to enhance the immune response. Learn more about plasmid DNA and viral vectors in oncology.
Immunotherapy Breakdown
What Immunotherapy Options Exist?
Monoclonal Antibodies (mAbs): Lab-made antibodies designed to target specific proteins on cancer cells, aiding in immune recognition.
Immune Checkpoint Inhibitors: Drugs that block proteins used by cancer cells to evade immune attacks, such as PD-1/PD-L1 or CTLA-4 inhibitors.
Cancer Vaccines: Vaccines that stimulate the immune system to recognize and attack cancer-specific antigens.
Adoptive Cell Transfer (ACT): A process where immune cells, like T-cells, are extracted, genetically modified or expanded, and reinfused into the patient.
Cytokines: Proteins like interleukins or interferons that boost immune activity.
Oncolytic Virus Therapy: Uses modified viruses that infect and kill cancer cells, triggering an immune response.
What Are Desired Outcomes For Immunotherapy?
Tumor Shrinkage or Elimination: The immune system targets and destroys cancer cells, leading to a reduction in tumor size or complete elimination.
Prolonged Survival: Patients may experience extended life expectancy due to improved immune response, even if the tumor does not completely disappear.
Durable Response: Some patients exhibit long-lasting responses, even after stopping treatment, due to immune memory.
Plasmid DNA and Viral Vector Based Immunotherapy
Immunotherapy approaches involving plasmid DNA and viral vectors including AAV, adenoviral, lentiviral, and retroviral, focus on modifying the immune system to recognize and fight diseases, especially cancer. These genetic materials are used to introduce therapeutic genes into the patient’s cells, enhancing the immune response.
In these therapies, plasmid DNA is often used for transient gene expression, while viral vectors vectors are preferred for more reliable delivery to target cells. Both approaches are key tools in advancing personalized immunotherapy treatments. Read more about plasmid DNA and viral vectors in precision medicine.
Plasmid DNA
How it works: Plasmid DNA is used to deliver specific cancer antigens into cells. Once inside, the cell machinery translates the DNA into proteins (antigens), which are then presented to the immune system. This stimulates an immune response against the tumor cells expressing these antigens.
Example: Plasmid DNA vaccines for melanoma, where the plasmid encodes melanoma-associated antigens (e.g., MART-1, gp100). Read more about plasmid DNA and viral vectors in vaccine development.
Outcome: Induces a targeted immune response to destroy cancer cells carrying the specific antigens.
Chimeric Antigen Receptor T-cell (CAR-T) Therapy (Lentiviral / Retroviral Vectors)
How it works: In CAR-T therapy, T-cells are genetically modified using lentiviral or retroviral vectors to express chimeric antigen receptors (CARs) that target specific antigens on cancer cells. The patient’s T-cells are harvested, modified ex vivo, and then reinfused to attack cancer cells.
Example: FDA-approved CAR-T therapies, such as Kymriah and Yescarta, use lentiviral vectors
Outcome: Highly specific immune attack on cancer cells, often leading to remission in blood cancers like leukemia and lymphoma.
T-cell Receptor (TCR) Therapy (Lentiviral / Retroviral Vectors)
How it works: Similar to CAR-T, TCR therapy involves genetically engineering T-cells to express receptors that can recognize tumor-specific antigens presented by the patient’s cells. The modification is often done using lentiviral or retroviral vectors to introduce the gene encoding the desired T-cell receptor.
Example: TCR-modified T-cells targeting antigens like NY-ESO-1, a cancer-testis antigen, in sarcomas and melanomas.
Outcome: Targeted immune responses that are highly effective for solid tumors and hematological malignancies.
Gene Editing for Immune Cells (Plasmid DNA and AAV / Adenoviral / Lentiviral / Retroviral Vectors)
How it works: Gene editing can involve lentiviral or retroviral vectors to introduce genes into immune cells to enhance their ability to fight cancer. Plasmid DNA may also be used to transiently express gene-editing machinery, such as CRISPR-Cas9, to make precise genetic modifications in immune cells.
Example: Editing T-cells to knock out inhibitory receptors like PD-1 (a checkpoint protein) or to introduce synthetic receptors that boost the immune response to cancer cells.
Outcome: More robust T-cell responses and enhanced ability to evade immune suppression by tumors.
Ex Vivo Dendritic Cell Vaccines (Plasmid DNA and Lentiviral Vectors)
How it works: Dendritic cells (DCs) are harvested from a patient, then transfected with plasmid DNA or lentiviral vectors encoding tumor antigens. The modified DCs are then reintroduced into the patient to stimulate a strong immune response by presenting these antigens to T-cells.
Example: Dendritic cell vaccines where DCs are loaded with plasmid DNA encoding tumor-associated antigens or transduced with lentiviral vectors for sustained antigen presentation.
Outcome: Enhanced T-cell activation and stronger anti-tumor immune responses.
Cytokine Gene Therapy (Plasmid DNA and Lentiviral Vectors)
How it works: This approach involves using plasmid DNA or lentiviral vectors to deliver genes encoding cytokines (e.g., IL-2, GM-CSF) to boost the immune response. These cytokines enhance immune cell activation and proliferation.
Example: Direct injection of plasmid DNA encoding IL-12 into tumor sites or using lentiviral vectors to transduce T-cells to produce immune-activating cytokines.
Outcome: Augments immune cell recruitment and activation, enhancing the overall anti-tumor immune response.
Vaccine Development (Plasmid DNA and AAV / Adenoviral Vectors)
How it works: AAV and adenoviral vectors deliver genes encoding disease-specific antigens. The vectors stimulate a strong immune response due to their intrinsic immunogenicity.
Example: Chimpanzee adenoviral vector expressing SARS-CoV-2 spike protein. Adenovirus serotype 26 expressing SARS-CoV-2 spike protein.
Outcome: Robust immune response to prevent infection or disease and high immunogenicity even in single-dose regimens.
Oncolytic Therapy (Plasmid DNA and AAV / Adenoviral Vectors)
How it works: These AAV and adenoviruses selectively replicate in and destroy tumor cells, while also releasing tumor antigens to activate systemic anti-tumor immunity.
Example: Oncolytic herpesvirus engineered to express GM-CSF, but adenoviral counterparts (e.g., DNX-2401) use similar mechanisms.
Outcome: Direct tumor destruction and stimulation of systemic anti-tumor immune response and durable immune memory to prevent metastasis or recurrence.
Molecular Cloning, Mutagenesis, AAV Packaging, Adenovirus Packaging, Lentivirus Packaging, Retrovirus Packaging, and CRISPR-Cas9 Services for Immunotherapy R&D
Our laboratory specializes in plasmid DNA and viral vector services for immunotherapy discovery phase research including:
If you have a question about your plasmid DNA and viral vector based immunotherapy research, contact our team.
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