Checkpoint inhibitors: What are they and how do they work?

We recently had a chance to sit down with a few of the Antibody Engineering and Therapeutics speakers to get an inside look into what they're working on and insights into their work.  We continue our interview series off with Omid Hamid, MD, Chief of Research, Immuno-Oncology at The Angeles Clinic and Research Institute.

Our first question for Dr. Hamid is:
Tell us about checkpoint inhibitors – what they are and how they work?

Dr. Hamid: Sure. Checkpoint inhibitors are the body’s way of activating or inactivating the immune system. Checkpoint proteins tell the immune system what to do. So, the signals can up-regulate an immune response so that they are activating checkpoints or down-regulate an immune response. Those are inhibiting checkpoints. So, checkpoint inhibitors are also known as “immune checkpoint modulators”. They are designed to lessen the effectiveness of these checkpoint proteins that are on immune cells or tumor cells. 

As we have recognized, these interactions between these checkpoint proteins located on tumors and on immune cells down-regulate or dampen our immune systems. By making these checkpoint inhibitors, we can block the interactions and release the suppression of the immune system. 

Our bodies should be able to eliminate cancer. Unfortunately, the complex relationships with the body’s immune system and the body’s immune response is not always the best at eliminating cancer cells. The key reason is that these tumors can create an immunosuppressive environment. When normal cells change into cancer cells they can up-regulate these checkpoint proteins and evade the body’s surveillance.

Dr. Hamid will be presenting The Promise of PD1 Checkpoint Inhibition for Multiple Solid Tumors on Wednesday, December 10 at the Antibody Engineering and Therapeutics event. For more information on his session and the rest of the program, download the agenda. As a reader of this blog, when you register to join us and mention code XD14172BLOGJP, you can save 20% off the standard rate.

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Delivering Safe, Effective Therapeutics: IIR’s Immunogenicity and Bioassays Conferences

Two events, one goal.

Bring safe and effective therapeutics to the patient faster with IIR’s Immunogenicity and Bioassays conferences. 

The complexity of developing effective biologic therapeutics require adequate analytical methodology to characterize both their physicochemical properties and biological activity. Reducing the risk of triggering unwanted immune responses must be considered early on in drug development. The events focus on the current practice of comprehensive characterization of biotherapeutics from their discovery through all stages of their development.

IIR invites you to join us October 20-22, 2014 in Boston, MA for two co-located events: 15th Annual Immunogenicity for Biotherapeutics and 10th Annual Bioassays and Bioanalytical Method Development.

Download the brochure to find out how to register for one or both events and see for yourself why these are two can't miss events.

Download the Immunogenicity Brochure

Download the Bioassays Brochure

Now, you can save $100 on the current rate for each event. Register here with code XP1938BLOG for the Immunogenicity for Biotherapeutics conference.  Register here with code XP1969BLOG for the Bioassays and Bioanalytical Method Development conference. 

Questions? Comments? Reach out at MMadarasz@iirusa.com. 

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Planning Our New Protein Aggregation Event Brings a Change in Behavior

By Scott Wallask
Conference Producer, IBC Life Sciences

Last week, I stopped using drugs past their “expires by” date.

There. I said it – and in stating so, I also imply that I previously ingested expired meds.

To me, it wasn’t the same as maybe drinking milk that was a few days old. That latter practice is disgusting, often smelly, and can probably get you sick.

However, I honestly thought that a flu-fighting gel capsule could exist for years and years without worry, suspended in a state of frozen perpetuity until my nose and throat needed it. After all, medication isn’t food and it isn’t going to go sour on you.

Well, my attitude changed as I started researching a conference that has since become IBC’s newest drug discovery offering, Protein Aggregation, Stability & Solubility. The event takes place June 4-6, 2014, at the Grand Hyatt Hotel in downtown San Francisco.

In the midst of my calls to aggregation experts and research on the topic, I remember leaving work one night feeling unnerved about the end results of aggregation. In the case of protein therapeutics, aggregation can manifest as tiny particles that are either formed by some sort of chemical reaction within the formulation or perhaps by leaching of the surrounding materials into the solution. Sometimes this degradation can take years to occur, thus the expiration dates.

A few discussions with clinicians told me that aggregation can result in unintended immune responses in patients and consumers, otherwise known as immunogenicity concerns. Granted, there’s a long leap between a flu capsule and a cancer-fighting drug in terms of what aggregation can lead to, but the connection was crystal clear to me: Expired drugs might actually not be safe to use.

Imagine that possibility lurking in the back of a biotech researcher’s mind at the start of the long road to a protein drug’s development. The aggregation risks evolve as you enter the upstream and downstream phases. Does the protein you’ve chose bear a heightened threat of aggregation occurring? Will the excipient you add during formulation create aggregates later on?

The lesson I take from developing our Protein Aggregation, Stability & Solubility program is to measure for aggregation, and then measure again a different way. You’ll hear that theme a lot on our agenda, whether you tackle aggregation from the protein engineering side or through cutting-edge analytical methods.

Check out our current list of sessions and see what interests you. This is shaping up to be one of the largest aggregation-themed gatherings ever, with more than 30 sessions taking place over three days.

My job was easy – I just threw out my expired meds. Your job – preventing aggregation from occurring in the first place – is a lot tougher. I know the speakers and topics at our meeting in San Francisco will make your jobs a bit easier in that regard.

Follow Scott on Twitter @Scott_biopharma

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Immunogenicity For Biotherapeutics Sessions Spotlight: Investigating the Host Immune Response through Multi-Parametric Measurements

Leading up to Immunogenicity for Biotherapeutics this April 17-19, 2012 in Washington, DC, we'll be highlighting some of the key sessions at this year's conference.  Today, we're looking at "Investigating the Host Immune Response through Multi-Parametric Measurements".

If a synthetic molecule is not designed just right, it could trigger the patient’s immune system; to make things more complicated, it could trigger either the innate immune response, or the adaptive immune response. Experts working on protein engineering need to know about both pathways and how their molecules will be perceived – but there is not an industry-wide “toolkit” allowing for quick and efficient sharing of insights and discoveries. Without this, there is a lot of redundant work in the biologics industry – which hurts all participants, even though they may normally be competitors, because unsafe drugs result in overall patient loss of confidence in the entire product class or type of therapy.

This session goes over good strategies for predicting what will set off the various types of immune response, and how the industry can best share insights for mutual gain.

Featured Session: Investigating the Host Immune Response through Multi-Parametric Measurements
Featured Speaker: Murli Krishna, PhD, Senior Research Investigator II, BRISTOL-MYERS SQUIBB
About the session: Successful development of your biotherapeutic depends on your ability to measure all of the perturbations that it may trigger in both the innate and adaptive arms of host immune response. This talk will explore the wide variety of experimental approaches for collecting qualitative and quantitative data that can best reflect such changes.

• • Discuss the needs and potential designs for an integrated cross-industry approach
• • Strategize for an open-sourced toolkit that would help the industry gain and share insights more quickly

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2010 DDP Awards: Technology Innovation Nominee: Wallace H. Coulter Center for Translational Research, University of Miami

Technology: a novel Nanoparticle which offers unique targeted in vivo delivery of nucleic acids into Antigen Presenting Cells (APC) resulting in robust / protective immune responses.

The platform is not only ideal for “Genetic Vaccination” as it targets APC and activates helper T cells, it, incidentally, may be used as delivery of nucleic acids including siRNA into such mononuclear cells which has broad therapeutic applications. Wallace H. Coulter Center of the University of Miami is a technology development center for biomedical innovation. WHCC is unique in acting as a catalyst for moving innovative University of Miami research with commercial potential from the bench to industry.

The winners will be announced at an awards ceremony on Tuesday, January 26 at the Drug Delivery Partnerships International Conference.

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