What have your Ph.D. studies focused on?
“The focus or the main aim of my Ph.D. has been to develop and use methods for phenotypic antibody discovery. Antibody drugs are a type of drug therapy that uses your body's immune system against diseases, including cancer. They work by recognizing and finding specific proteins or targets on cancer cells. Many antibody-based products have been approved for use with many more in clinical trials. They are the fastest-growing drugs on the market. Although there tend to be many antibodies for the most popular targets, so there remains a great need to find new targets. This kind of phenotypic discovery process would help with that.
In the phenotypic discovery process, you develop antibodies based on function instead of using a target-based approach. This means that we develop antibodies without knowing the protein target and instead we develop antibodies based on their function. For example, you have a cancer cell, and you want antibodies that can kill the cancer cell or activate a certain immune cell or so on, and then you develop the antibodies based on this. When you find antibodies with the desired function, then you try to figure out what the actual protein target is afterward, because that's needed before you can enter clinical trials.
In my first paper, we describe the entire antibody discovery process where we developed antibodies capable of depleting chronic lymphocytic leukemia (CLL) cells using primary cells obtained from patients. CLL is considered the most common form of leukemia in adults and is a type of cancer that starts in white blood cells, known as lymphocytes.
The other aspects of my thesis, have built off this initial work, focusing on the different steps of the discovery process. In one project we focused on the enrichment of antibodies. Before you can test antibodies functionally, you have to enrich them from phage display libraries that house billions of antibodies. Of course, it’s not possible to test the function of billions of antibodies so you need to enrich your library for antibodies that are specific to the cell you are looking at. Typically, when you do that, the process is biased so that you would almost exclusively get antibodies that are targeting highly expressed receptors. So, we've developed a method that can help one dig deeper into the possible targets by enabling the detection of antibodies against more lowly expressed receptors. This gives you a bigger repertoire of antibodies against different receptors to test.
In another project, we used CRISPR technology for antibody target deconvolution or to identify the actual protein target. In the last project, we also used CRISPR, but in a different way. Antibodies for cancer treatment can either target cancer cells or immune cells within the tumor microenvironment to try and activate them against the tumor. One of the cell types that you could target is macrophages which usually have a pro-tumorigenic, immune suppressive phenotype within a tumor. Queues within the tumor microenvironment tend to direct these cells into this phenotype since macrophages can polarize easily from being immune suppressive to being immune activated. One possible way to treat cancer would be to activate these immune suppressive macrophages so that they are fighting the tumor instead of supporting it. So, in the last project, we looked at the mechanisms that are involved in macrophage polarization to try and see if there's something we can work on or target.
Ultimately, the goal is to use these methods to aid in the development of new drug options for patients with cancer,” explained Jenny.
Can you tell us more about the cover of your thesis?
“The cover of my thesis is inspired by the things that we worked with most throughout my time as a Ph.D. student. On the cover you can see that antibodies and Cas9 molecules are represented. It was designed by my daughter - she is great at drawing, and I thought it would be nice to involve her in this process,” noted Jenny.
How did you end up doing a Ph.D. at Lund Stem Cell Center?
“I took my master's years ago and have since been working with a biotech company called BioInvent based at Ideon in Lund for the last 20+ years. At BioInvent we develop antibody-based drugs for cancer therapy, and we have several antibody-based products in clinical trials. We have this pipeline where we do phenotypic antibody discovery. So, part of the reason why I joined Björn’s group was this idea that we wanted to explore – whether CRISPR could be used in this discovery process. Björn has been working with CRISPR for some time, so it just made sense to come here. It also made sense for me to take the next step and pursue a doctoral degree because in the drug industry, once you reach a certain point, it can be difficult to get any further if you don't have a Ph.D. So, in 2016, I had worked a while after having my third kid and felt that I was ready to try something new. At that time, my colleagues at BioInvent suggested that it was maybe time to get my Ph.D., so I decided it was time to do just that.
So, in 2016 I joined Björn Nilsson’s research group which focuses on genetic variation influencing blood cell formation and blood cancer risk in humans, as a part-time Ph.D. student. At the same time, I’ve also remained employed at BioInvent throughout my Ph.D., so I’ve had one foot here at BMC and one foot at Bioinvent,” detailed Jenny.
What have you found the most enjoyable during your Ph.D. studies?
“What have I enjoyed most? Well, I mentioned earlier this last project with macrophages. That was just an idea that I had when I was doing my research and thought it would be cool to test. Björn agreed and so I got to explore that idea. I had a master student who did most of the lab work, but the fact that you know, it's been free to just come up with an idea and do it. I enjoyed that freedom. There is some freedom in the industry as well, but there you're more controlled by deadlines and plans which we’re meant to follow and not stray from. But here in academia, you can kind of go in the direction that you want, and I think that is a nice thing to be able to do, to just go for it.
I’ve also had the pleasure of being part of an encouraging environment and have enjoyed working with a great mix of people from all over the world. I’ve also really enjoyed the fact that we don't do the same thing and that I was able to work within a group that does something completely different from what we do at BioInvent. I mean we're still working with cancer and blood or hematological cancers but in totally different ways. So that's also been very nice to experience,” highlighted Jenny.
What has been the most challenging aspect?
“To be honest, I haven't found anything really challenging. It's just been fun, and everything has just worked out well. I think maybe coming from working almost 20 years in research, I was already used to the fact that sometimes the lab work doesn't always work the way it was meant to, and you have to take another course. So, in that way, I was kind of prepared for that already. Of course, the pandemic made things a little bit more complicated, but I think we also learned how to work around it nicely,” noted Jenny.
What are your plans following your Ph.D. defense?
“I'm going back to BioInvent full-time now. There is a new position for me, so that is very exciting. While I’ve enjoyed my time in academia, I’ve realized that I am more of an industry person. I miss the faster pace of things where many people are focused on the same goal, making the road to discovery much faster. So, I am looking forward to getting back to that,” reflected Jenny.
Any tips or advice for future Ph.D. students?
“I think mainly to remind them to enjoy themselves throughout the Ph.D. process – it’s fun and they shouldn’t stress too much about the little things. I think also to try and plan ahead so that things are not left for the last minute. I think that will help to make their time as a Ph.D. student more enjoyable,” concluded Jenny.