Precise drug screening for personalized cancer treatment
A mixture and equipment technology, applied in the screening of compounds, specific-purpose bioreactors/fermenters, library screening, etc., can solve the slow amplification and operation of PDMC models, loss of tissue composition and clonal diversity, and inhomogeneity Size and other issues
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[0212] Figure 20 and 21 Another example of an apparatus for forming a plurality of micro-organ spheroids as described herein is shown. exist Figure 20 In the device, the device may include a plurality of micro-organ spheres forming a junction where an immiscible material (eg, oil) 2002 may be added to a reservoir and / or port 2004 in the device. Similarly, unpolymerized material 2006 (in this example, including dissociated biopsy cells and fluid matrix material) may be added to a reservoir or port 2008 in the device. In some variations, a second or additional material (eg, a bioactive agent) can be added through the third set of ports 2010 . These components can combine at junctions (similar to those described above), forming droplets in immiscible materials that can polymerize into micro-organspheres. exist Figure 20 In , three (or more) parallel junctions with corresponding inputs and outputs are shown.
[0213] Figure 21 shows the use of Figure 20 The device sho...
Embodiment 2
[0215] Example 2: screening results
[0216] As described above, patient-derived micro-organspheres and their methods for screening pharmaceutical compositions can be used to accurately predict the response of a patient's tumor to one or more drug treatments. In some cases, the use of micro-organspheres may provide accurate results where traditional culture-based drug screening cannot accurately predict drug response. For example, in Figures 22A-22D In , micro-organspheres (rather than cell lines) can be correlated with patient response. exist Figure 22A In , traditional cell lines given drugs such as oxaliplatin were examined; this drug line showed no effect, and tumors were predicted to be resistant to the drug across all dose ranges examined.
[0217] For comparison, multiple micro-organspheres were generated from patient biopsy samples, as Figure 22B shown. In this example, patient-derived micro-organspheres showed significantly reduced cell survival in tumor micro...
Embodiment 3
[0218] Example 3: Correlation between Micro-Organspheres and Patient Response
[0219] In a similar set of experiments, micro-organspheres were generated from biopsy material ( Figure 23A ), and use the obtained micro-organ spheres for drug effect screening. Figure 23B The effect of the first drug (oxaliplatin) on these micro-organspheres is shown showing no change in the percent survival of the micro-organspheres in the presence of the drug, predicting drug resistance. Similarly, treatment with a second drug, irinotecan, showed a lack of effect on micro-organspheres, predicting drug resistance, as Figure 23C shown. The patient received concurrent treatment with oxaliplatin and irinotecan and showed no response after 6 months of treatment. Thus, micro-organspheres are highly correlated with patient response to standard-of-care medications. In this case, the patient experienced six months of side effects and toxicity that could have been avoided by the predicted response...
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